Georges Vauquelin

Summary

Affiliation: Vrije Universiteit Brussel
Country: Belgium

Publications

  1. pmc Exploring avidity: understanding the potential gains in functional affinity and target residence time of bivalent and heterobivalent ligands
    Georges Vauquelin
    Department Molecular and Biochemical Pharmacology, Vrije Universiteit Brussel, Brussels, Belgium
    Br J Pharmacol 168:1771-85. 2013
  2. doi request reprint Simplified models for heterobivalent ligand binding: when are they applicable and which are the factors that affect their target residence time
    Georges Vauquelin
    Department of Molecular and Biochemical Pharmacology, Vrije Universiteit Brussel, Pleinlaan 2, 1050, Brussels, Belgium
    Naunyn Schmiedebergs Arch Pharmacol 386:949-62. 2013
  3. ncbi request reprint Rebinding: or why drugs may act longer in vivo than expected from their in vitro target residence time
    Georges Vauquelin
    Free University Brussels VUB, Department of Molecular and Biochemical Pharmacology, Building E 5 10, Pleinlaan 2, B 1050 Brussels, Belgium 32 2 6291955 32 2 6291358
    Expert Opin Drug Discov 5:927-41. 2010
  4. doi request reprint Radioligand dissociation measurements: potential interference of rebinding and allosteric mechanisms and physiological relevance of the biological model systems
    Georges Vauquelin
    Free University Brussels VUB, Molecular and Biochemical Pharmacology Department, Brussels, Belgium
    Expert Opin Drug Discov 7:583-95. 2012
  5. doi request reprint Clozapine, atypical antipsychotics, and the benefits of fast-off D2 dopamine receptor antagonism
    Georges Vauquelin
    Department of Molecular and Biochemical Pharmacology, Vrije Universiteit Brussel, Pleinlaan 2, 1050, Brussels, Belgium
    Naunyn Schmiedebergs Arch Pharmacol 385:337-72. 2012
  6. ncbi request reprint A two-state receptor model for the interaction between angiotensin II type 1 receptors and non-peptide antagonists
    G Vauquelin
    Department of Molecular and Biochemical Pharmacology, Free University of Brussels VUB, Sint Genesius Rode, Belgium
    Biochem Pharmacol 61:277-84. 2001
  7. ncbi request reprint New insights in insurmountable antagonism
    G Vauquelin
    Department of Molecular and Biochemical Pharmacology, Free University of Brussels VUB, Sint Genesius Rode, Belgium
    Fundam Clin Pharmacol 16:263-72. 2002
  8. ncbi request reprint Long-lasting angiotensin type 1 receptor binding and protection by candesartan: comparison with other biphenyl-tetrazole sartans
    Georges Vauquelin
    Department of Molecular and Biochemical Pharmacology, Free University of Brussels VUB, Brussels, Belgium
    J Hypertens Suppl 24:S23-30. 2006
  9. ncbi request reprint Slow antagonist dissociation and long-lasting in vivo receptor protection
    Georges Vauquelin
    Department of Molecular and Biochemical Pharmacology, Vrije Universiteit Brussel, Pleinlaan 2, B 1050 Brussels, Belgium
    Trends Pharmacol Sci 27:356-9. 2006
  10. ncbi request reprint Kinetic versus allosteric mechanisms to explain insurmountable antagonism and delayed ligand dissociation
    Georges Vauquelin
    Department of Molecular and Biochemical Pharmacology, Free University of Brussels VUB, Building E 5 10, Pleinlaan 2, Brussel B 1050, Belgium
    Neurochem Int 51:254-60. 2007

Collaborators

Detail Information

Publications71

  1. pmc Exploring avidity: understanding the potential gains in functional affinity and target residence time of bivalent and heterobivalent ligands
    Georges Vauquelin
    Department Molecular and Biochemical Pharmacology, Vrije Universiteit Brussel, Brussels, Belgium
    Br J Pharmacol 168:1771-85. 2013
    ..In in vitro experiments, the manifestation of steep saturation curves and of accelerated dissociation in the presence of competitive ligands could mistakenly be interpreted as evidence for non-competitive, allosteric interactions...
  2. doi request reprint Simplified models for heterobivalent ligand binding: when are they applicable and which are the factors that affect their target residence time
    Georges Vauquelin
    Department of Molecular and Biochemical Pharmacology, Vrije Universiteit Brussel, Pleinlaan 2, 1050, Brussels, Belgium
    Naunyn Schmiedebergs Arch Pharmacol 386:949-62. 2013
    ..Hence, the presence of a slow-associating pharmacophore could be counterproductive. Yet, a long residence time is unfortunately also responsible for the slow attainment of binding equilibrium. ..
  3. ncbi request reprint Rebinding: or why drugs may act longer in vivo than expected from their in vitro target residence time
    Georges Vauquelin
    Free University Brussels VUB, Department of Molecular and Biochemical Pharmacology, Building E 5 10, Pleinlaan 2, B 1050 Brussels, Belgium 32 2 6291955 32 2 6291358
    Expert Opin Drug Discov 5:927-41. 2010
    ..Intact cell radioligand dissociation and related ex vivo experiments offer useful indications about a drug's aptitude to experience target rebinding...
  4. doi request reprint Radioligand dissociation measurements: potential interference of rebinding and allosteric mechanisms and physiological relevance of the biological model systems
    Georges Vauquelin
    Free University Brussels VUB, Molecular and Biochemical Pharmacology Department, Brussels, Belgium
    Expert Opin Drug Discov 7:583-95. 2012
    ..To this end, radioligand dissociation experiments are often carried out on in vitro models, such as intact cells and the membranes thereof, but the interpretation of the collected data is sometimes ambiguous...
  5. doi request reprint Clozapine, atypical antipsychotics, and the benefits of fast-off D2 dopamine receptor antagonism
    Georges Vauquelin
    Department of Molecular and Biochemical Pharmacology, Vrije Universiteit Brussel, Pleinlaan 2, 1050, Brussels, Belgium
    Naunyn Schmiedebergs Arch Pharmacol 385:337-72. 2012
    ..Attention is also drawn to the divergent residence times of hydrophobic antagonists like haloperidol when comparing radioligand binding data on cell membranes with those on intact cells and clinical data...
  6. ncbi request reprint A two-state receptor model for the interaction between angiotensin II type 1 receptors and non-peptide antagonists
    G Vauquelin
    Department of Molecular and Biochemical Pharmacology, Free University of Brussels VUB, Sint Genesius Rode, Belgium
    Biochem Pharmacol 61:277-84. 2001
    ..In conclusion, these findings provide further support for the concept that insurmountable and surmountable AT1 antagonists are mutually competitive and that insurmountable antagonist-receptor complexes may adopt different states...
  7. ncbi request reprint New insights in insurmountable antagonism
    G Vauquelin
    Department of Molecular and Biochemical Pharmacology, Free University of Brussels VUB, Sint Genesius Rode, Belgium
    Fundam Clin Pharmacol 16:263-72. 2002
    ..New experimental approaches, such as intact cell studies and the use of computer-assisted simulations based on dynamic receptor models, herald the advent of better insight in the future...
  8. ncbi request reprint Long-lasting angiotensin type 1 receptor binding and protection by candesartan: comparison with other biphenyl-tetrazole sartans
    Georges Vauquelin
    Department of Molecular and Biochemical Pharmacology, Free University of Brussels VUB, Brussels, Belgium
    J Hypertens Suppl 24:S23-30. 2006
    ..The proportion of insurmountable antagonism, the potency and the dissociation rate of the BTsartans decreases in the order: candesartan > EXP3174 (losartan's active metabolite) > valsartan > irbesartan >> losartan...
  9. ncbi request reprint Slow antagonist dissociation and long-lasting in vivo receptor protection
    Georges Vauquelin
    Department of Molecular and Biochemical Pharmacology, Vrije Universiteit Brussel, Pleinlaan 2, B 1050 Brussels, Belgium
    Trends Pharmacol Sci 27:356-9. 2006
    ..However, when the half-life of the free antagonist prevails, longer effective protection by slowly dissociating antagonists occurs only if the receptor is exposed to rapid fluctuations in free agonist concentration...
  10. ncbi request reprint Kinetic versus allosteric mechanisms to explain insurmountable antagonism and delayed ligand dissociation
    Georges Vauquelin
    Department of Molecular and Biochemical Pharmacology, Free University of Brussels VUB, Building E 5 10, Pleinlaan 2, Brussel B 1050, Belgium
    Neurochem Int 51:254-60. 2007
    ..On the other hand, these observations can also be explained by negative allosteric interactions among topographically distinct ligand binding sites at the same receptor or di/multimeric receptor complex...
  11. doi request reprint Ligands, their receptors and ... plasma membranes
    G Vauquelin
    Department of Molecular and Biochemical Pharmacology, Institute for Molecular Biology and Biotechnology, Vrije Universiteit Brussel VUB, Pleinlaan 2, B 1050 Brussel, Belgium
    Mol Cell Endocrinol 311:1-10. 2009
    ..Pharmacologists focused attention at ligand concentrations in membrane, their adsorption and release rates and the effects thereof on ligand potency and residence time at the receptor...
  12. pmc Long-lasting target binding and rebinding as mechanisms to prolong in vivo drug action
    Georges Vauquelin
    Department of Molecular and Biochemical Pharmacology, Vrije Universiteit Brussel, Brussels, Belgium
    Br J Pharmacol 161:488-508. 2010
    ..By mimicking the complexity of tissues, intact cells offer the opportunity to investigate both mechanisms under the same, physiologically relevant conditions...
  13. ncbi request reprint The effects of candesartan on human AT1 receptor-expressing Chinese hamster ovary cells
    G Vauquelin
    Department of Molecular and Biochemical Pharmacology, Institute of Molecular Biology, Free University of Brussels VUB, Sint Genesius Rode, Belgium
    J Am Soc Nephrol 10:S15-7. 1999
    ..The insurmountable effect of candesartan can therefore be ascribed to its long-lasting inhibition of the AT1 receptor...
  14. ncbi request reprint Models and methods for studying insurmountable antagonism
    Georges Vauquelin
    Dept of Molecular and Biochemical Pharmacology, Institute for Molecular Biology and Biotechnology, Free University of Brussels VUB, Paardenstraat 65, B 1640 Sint Genesius Rode, Belgium
    Trends Pharmacol Sci 23:514-8. 2002
    ..Intact cell studies allow greater flexibility and tighter control of the experimental conditions and therefore have the potential to offer a better insight into the molecular basis of insurmountable antagonism...
  15. ncbi request reprint Angiotensin AT4 receptor ligand interaction with cystinyl aminopeptidase and aminopeptidase N: [125I]Angiotensin IV only binds to the cystinyl aminopeptidase apo-enzyme
    Heidi Demaegdt
    Research Group on Experimental Pharmacology, Department of Molecular and Biochemical Pharmacology, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium
    Eur J Pharmacol 546:19-27. 2006
    ..We provide evidence that CAP predominates in these cell lines and that, comparatively, CHO-K1 cells display the highest level of this enzyme...
  16. ncbi request reprint Ligand binding and functional properties of human angiotensin AT1 receptors in transiently and stably expressed CHO-K1 cells
    Minh Tam Le
    Department of Molecular and Biochemical Pharmacology, Institute for Molecular Biology and Biotechnology, Vrije Universiteit Brussel VUB, Belgium
    Eur J Pharmacol 513:35-45. 2005
    ..Confocal microscopy revealed rapid internalization induced by angiotensin II and sarile but not by candesartan. The above disparities may result from differences in receptor maturation and/or cellular surrounding...
  17. pmc Metal ion modulation of cystinyl aminopeptidase
    Hilde Laeremans
    Department of Molecular and Biochemical Pharmacology, Vrije Universiteit Brussel, Pleinlaan 2, B 1050 Brussels, Belgium
    Biochem J 390:351-7. 2005
    ..These findings support the concept that high-affinity [125I]angiotensin IV binding, previously referred to as 'AT4 receptor binding', only occurs for the cystinyl aminopeptidase apoenzyme...
  18. ncbi request reprint A two-state model of antagonist-AT1 receptor interaction: further support by binding studies at low temperature
    Ilse Verheijen
    Department of Molecular and Biochemical Pharmacology, Free University of Brussels VUB, Building E, 2 Pleinlaan, Belgium
    Biochem Pharmacol 65:1339-41. 2003
    ..This gave the opportunity to verify the two-state model for the first time with experimental data...
  19. doi request reprint Binding of "AT4 receptor" ligands to insulin regulated aminopeptidase (IRAP) in intact Chinese hamster ovary cells
    Heidi Demaegdt
    Department of Molecular and Biochemical Pharmacology, Research Group of Experimental Pharmacology, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium
    Mol Cell Endocrinol 339:34-44. 2011
    ..The in vivo efficacy of stable and unstable "AT(4)-receptor" ligands could therefore differ...
  20. doi request reprint Selective labeling of IRAP by the tritiated AT(4) receptor ligand [3H]Angiotensin IV and its stable analog [3H]AL-11
    Heidi Demaegdt
    Research Group of Experimental Pharmacology, Department of Molecular and Biochemical Pharmacology, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium
    Mol Cell Endocrinol 311:77-86. 2009
    ..This confirms that the active and apo-forms of IRAP have a distinct pharmacological profile...
  21. ncbi request reprint Peptide and nonpeptide antagonist interaction with constitutively active human AT1 receptors
    Minh Tam Le
    Department of Molecular and Biochemical Pharmacology, Institute for Molecular Biology and Biotechnology, Vrije Universiteit Brussel VUB, Pleinlaan 2, Belgium
    Biochem Pharmacol 65:1329-38. 2003
    ....
  22. doi request reprint Angiotensin IV displays only low affinity for native insulin-regulated aminopeptidase (IRAP)
    Heidi Demaegdt
    Research Group of Experimental Pharmacology, Department of Molecular and Biochemical Pharmacology, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium
    Fundam Clin Pharmacol 26:194-7. 2012
    ..By using 7B along with the new stable Ang IV-analog [(3) H]AL-11, we here show that the native enzyme is only a low-affinity target for Ang IV...
  23. ncbi request reprint Synergistic inhibition of the enzymatic activity of aminopeptidase N by divalent metal ion chelators
    Patrick M L Vanderheyden
    Department of Molecular and Biochemical Pharmacology, Vrije Universiteit Brussel, Pleinlaan 2, B 1050 Brussels, Belgium
    Fundam Clin Pharmacol 20:613-9. 2006
    ..Compatible with this model, Ca2+ may bind to this allosteric site resulting in the potentiation of Zn2+-mediated re-activation of the enzyme activity in the presence of EDTA and 1,10-phenanthroline...
  24. doi request reprint Conformational constraints in angiotensin IV to probe the role of Tyr², Pro⁵ and Phe⁶
    Aneta Lukaszuk
    Department of Organic Chemistry, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium
    J Pept Sci 17:545-53. 2011
    ..These results confirm the importance of conformational constrained amino acids to generate selectivity in bioactive peptides...
  25. ncbi request reprint Endogenous cystinyl aminopeptidase in Chinese hamster ovary cells: characterization by [125I]Ang IV binding and catalytic activity
    Heidi Demaegdt
    Research Group on Experimental Pharmacology, Department of Molecular and Biochemical Pharmacology, Vrije Universiteit Brussel, Pleinlaan 2, Brussels 1050, Belgium
    Biochem Pharmacol 68:885-92. 2004
    ..This difference in potency varied from one peptide to another. These pharmacological properties match those previously reported for the recombinantly-expressed human cystinyl aminopeptidase in embryonal kidney cells...
  26. ncbi request reprint Synergistic modulation of cystinyl aminopeptidase by divalent cation chelators
    Heidi Demaegdt
    Research Group on Experimental Pharmacology, Department of Molecular and Biochemical Pharmacology, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium
    Biochem Pharmacol 68:893-900. 2004
    ..Modulation of the effects of 1,10-PHE by other chelators such as EDTA or EGTA, suggests that, in addition to the binding site for zinc in the catalytic site, cystinyl aminopeptidase also bears a regulatory divalent cation binding site...
  27. ncbi request reprint Effect of saponin and filipin on antagonist binding to AT 1 receptors in intact cells
    Ilse Verheijen
    Department of Molecular and Biochemical Pharmacology, Free University of Brussels VUB, Pleinlaan 2, 1050 Brussels, Belgium
    Biochem Pharmacol 67:1601-6. 2004
    ..This suggests that the intracellular composition and/or organisation of living cells play an active role with regard to antagonist-AT1 receptor interactions...
  28. ncbi request reprint Antagonist interaction with endogenous AT(1) receptors in human cell lines
    Ilse Verheijen
    Department of Molecular and Biochemical Pharmacology, Free University of Brussels VUB, 65 Paardenstraat, B 1640 Sint Genesius Rode, Belgium
    Biochem Pharmacol 64:1207-14. 2002
    ..The similar binding and inhibitory properties of these antagonists among the investigated cell types validates the use of CHO-hAT(1) cells for investigating pharmacological properties of human AT(1) receptors...
  29. doi request reprint [3H]IVDE77, a novel radioligand with high affinity and selectivity for the insulin-regulated aminopeptidase
    Alexandros Nikolaou
    Molecular and Biochemical Pharmacology, Vrije Universiteit Brussel, Building E, Pleinlaan 2, B 1050 Brussels, Belgium
    Eur J Pharmacol 702:93-102. 2013
    ..In summary, IVDE77 is a useful tool for the detection of IRAP under physiological conditions, and may contribute to elucidating the mechanism of Ang IV to ascertain which functions are IRAP-dependent...
  30. doi request reprint Beta-homo-amino acid scan of angiotensin IV
    Aneta Lukaszuk
    Department of Organic Chemistry, Department of Molecular and Biochemical Pharmacology, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium
    J Med Chem 51:2291-6. 2008
    ....
  31. doi request reprint Involvement of the AT1 receptor subtype in the effects of angiotensin IV and LVV-haemorphin 7 on hippocampal neurotransmitter levels and spatial working memory
    Dimitri De Bundel
    Research Group Experimental Pharmacology, Department of Pharmaceutical Chemistry, Drug Analysis and Drug Information, Vrije Universiteit Brussel, Brussels, Belgium
    J Neurochem 112:1223-34. 2010
    ..c.v. injection, suggesting an extrahippocampal site of action. We propose that AT1 receptors are implicated in the neurochemical and cognitive effects of Ang IV, whereas LVV-H7 may mediate its effects via IRAP...
  32. ncbi request reprint Metabolism of angiotensin II is required for its in vivo effect on dopamine release in the striatum of the rat
    Bart Stragier
    Department of Pharmaceutical Chemistry and Drug Analysis, Research Group Experimental Pharmacology, Vrije Universiteit Brussel, Brussels, Belgium
    J Neurochem 90:1251-7. 2004
    ..We propose a role for IRAP as mediator for the effects of Ang IV and related peptides on extracellular dopamine levels in the striatum of the rat...
  33. doi request reprint The replacement of His(4) in angiotensin IV by conformationally constrained residues provides highly potent and selective analogues
    Aneta Lukaszuk
    Department of Organic Chemistry, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium
    J Med Chem 52:5612-8. 2009
    ....
  34. doi request reprint Antagonist-radioligand binding to D2L-receptors in intact cells
    Ann Packeu
    Free University of Brussels VUB, Department of Molecular and Biochemical Pharmacology, Institute for Molecular Biology and Biotechnology, Pleinlaan 2, B 1050 Brussels, Belgium
    Biochem Pharmacol 75:2192-203. 2008
    ..To integrate these new findings, a model is proposed in which raclopride approaches the receptor from the aqueous phase, while spiperone approaches the receptor by lateral diffusion within the membrane...
  35. ncbi request reprint Involvement of insulin-regulated aminopeptidase in the effects of the renin-angiotensin fragment angiotensin IV: a review
    Bart Stragier
    Department of Pharmaceutical Chemistry, Drug Analysis and Drug Information, Research Group Experimental Pharmacology, Vrije Universiteit Brussel, Brussels, Belgium
    Heart Fail Rev 13:321-37. 2008
    ..On the other hand, a wide range of studies have made it clear that IRAP might become an important target for drug development against different pathologies such as Alzheimer's disease, epilepsy and ischemia...
  36. doi request reprint Non-competitive interaction between raclopride and spiperone on human D-receptors in intact Chinese hamster ovary cells
    Ann Packeu
    Department of Molecular and Biochemical Pharmacology, Institute for Molecular Biology and Biotechnology, Free University of Brussels VUB, Pleinlaan 2, B 1050 Brussels, Belgium
    Fundam Clin Pharmacol 24:283-91. 2010
    ..These new findings could point at the occurrence of allosteric interactions between different classes of D(2)-receptor antagonists...
  37. pmc Molecular characterisation of the interactions between olmesartan and telmisartan and the human angiotensin II AT1 receptor
    M T Le
    Departments of Molecular and Biochemical Pharmacology, Free University of Brussels VUB, Pleinlaan 2, B 1050 Brussels, Belgium
    Br J Pharmacol 151:952-62. 2007
    ..This study compared the molecular interactions of olmesartan and telmisartan with the human AT(1) receptor, using well characterised in vitro methods and model systems...
  38. doi request reprint Pressor and renal hemodynamic effects of the novel angiotensin A peptide are angiotensin II type 1A receptor dependent
    Rui Yang
    Department of Pharmacology, Vrije Universiteit Brussel, Laarbeeklaan 103, B 1090 Brussels, Belgium
    Hypertension 57:956-64. 2011
    ..Overall, the responses to Ang A and Ang II were similar. Ang A has no physiological role to modulate the pressor and renal hemodynamic effects of Ang II...
  39. doi request reprint Amino triazolo diazepines (Ata) as constrained histidine mimics
    Koen Buysse
    Laboratory of Organic Chemistry, Vrije Universiteit Brussel, Pleinlaan 2, B 1050 Brussels, Belgium
    Org Lett 13:6468-71. 2011
    ....
  40. doi request reprint Antagonist-D2S-dopamine receptor interactions in intact recombinant Chinese hamster ovary cells [corrected]
    Ann Packeu
    Department of Molecular and Biochemical Pharmacology, Institute for Molecular Biology and Biotechnology, Free University of Brussels VUB, Pleinlaan 2, B 1050 Brussels, Belgium
    Fundam Clin Pharmacol 24:293-303. 2010
    ..These different modes of approach could imply the existence of topologically distinct ligand binding sites at D(2)-receptors...
  41. ncbi request reprint Distinct binding properties of the AT(1) receptor antagonist [(3)H]candesartan to intact cells and membrane preparations
    Frederik L P Fierens
    Department of Molecular and Biochemical Pharmacology, Free University of Brussels VUB, 65 Paardenstraat, B 1640 Sint Genesius Rode, Belgium
    Biochem Pharmacol 63:1273-9. 2002
    ..Whereas the binding was almost completely enthalpy-driven on intact cells, there was a mixed contribution of both enthalpy and entropy on membranes...
  42. ncbi request reprint Effects of BIBP3226 and BIBP3435 on cytosolic calcium in neuropeptide Y Y1 receptor-transfected Chinese hamster ovary cells and wild type CHO-K1 cells
    P M Vanderheyden
    Department of Molecular and Biochemical Pharmacology, Free University of Brussels (VUB, Paardenstraat 65, B-1640 Sint-Genesius Rode, Belgium
    J Recept Signal Transduct Res 21:11-23. 2001
    ....
  43. ncbi request reprint Cellular targets for angiotensin II fragments: pharmacological and molecular evidence
    Georges Vauquelin
    Department of Molecular and Biochemical Pharmacology, Vrije Universiteit Brussel VUB, Sint Genesius, Rode, B 1640, Belgium
    J Renin Angiotensin Aldosterone Syst 3:195-204. 2002
    ....
  44. ncbi request reprint Angiotensin IV is a potent agonist for constitutive active human AT1 receptors. Distinct roles of the N-and C-terminal residues of angiotensin II during AT1 receptor activation
    Minh Tam Le
    Department of Molecular and Biochemical Pharmacology, Institute of Molecular Biology and Biotechnology, Vrije Universiteit Brussel, B 1640 Sint Genesius Rode, Belgium
    J Biol Chem 277:23107-10. 2002
    ..The receptor adopts a more relaxed conformation, allowing the binding of the C-terminal five residues of Ang II that switches this "preactivated" receptor into the fully active conformation...
  45. ncbi request reprint Identification and characterization of imidazoline-binding sites from calf striatum
    E Czerwiec
    Department of Protein Chemistry, Institute for Molecular Biology and Biotechnology, Free University of Brussels VUB, St Genesius Rode, Belgium
    Eur J Pharmacol 315:99-109. 1996
    ..The venom of the marine snail Conus geographus is the most potent of the 13 tested Conus venom preparations. None of the tested venoms is able to discriminate between both sites...
  46. ncbi request reprint Effect of BIBP3226 on inositol phosphate accumulation and cytosolic calcium level in control and NPY Y1 receptor expressing CHO-K1 cells
    P M Vanderheyden
    Department of Protein Chemistry, Free University of Brussels VUB, Sint Genesius Rode, Belgium
    Regul Pept 75:191-9. 1998
    ..This effect of BIBP3226 is likely to be mediated by activation of an until now unknown receptor or cellular target that is endogeneously expressed in CHO-K1 cells...
  47. pmc Distinction between surmountable and insurmountable selective AT1 receptor antagonists by use of CHO-K1 cells expressing human angiotensin II AT1 receptors
    P M Vanderheyden
    Department of Protein Chemistry, Free University of Brussels VUB, Sint Genesius Rode, Belgium
    Br J Pharmacol 126:1057-65. 1999
    ....
  48. ncbi request reprint Insurmountable angiotensin AT1 receptor antagonists: the role of tight antagonist binding
    F L Fierens
    Department of Molecular and Biochemical Pharmacology, Free University of Brussels VUB, Belgium
    Eur J Pharmacol 372:199-206. 1999
    ..Our data indicate that antagonist-receptor complexes are divided into a fast reversible/surmountable population and a tight binding/insurmountable population at the very onset of the incubation with angiotensin II...
  49. ncbi request reprint Tight binding of the angiotensin AT(1) receptor antagonist
    F L Fierensa
    Department of Molecular and Biochemical Pharmacology, Institute for Molecular Biology, Free University of Brussels, Paardenstraat 65, B 1640, Sint Genesius Rode, Belgium
    Biochem Pharmacol 61:1227-35. 2001
    ..Insurmountable antagonism of candesartan is therefore independent from receptor internalization via clathrin-coated pits...
  50. ncbi request reprint Reversible and syntopic interaction between angiotensin receptor antagonists on Chinese hamster ovary cells expressing human angiotensin II type 1 receptors
    P M Vanderheyden
    Department of Molecular Pharmacology, Free University of Brussels, Sint Genesius Rode, Belgium
    Biochem Pharmacol 59:927-35. 2000
    ..In addition, similar kinetic data were obtained from the slowing of the [(3)H]candesartan association rate to antagonist preincubated cells...
  51. ncbi request reprint Binding characteristics of [(3)H]-irbesartan to human recombinant angiotensin type 1 receptors
    P M Vanderheyden
    Department of Molecular and Biochemical Pharmacology, Free University of Brussels, Rode, B 1640, Belgium
    J Renin Angiotensin Aldosterone Syst 1:159-65. 2000
    ..In contrast, other phenomena such as the plasma half life and tissue-related factors are necessary to explain its sustained in vivo antihypertensive effect...
  52. ncbi request reprint Angiotensin II type 1 receptor antagonists. Why do some of them produce insurmountable inhibition?
    P M Vanderheyden
    Department of Molecular and Biochemical Pharmacology, Free University of Brussels, Sint Genesius Rode, Belgium
    Biochem Pharmacol 60:1557-63. 2000
    ..In addition to the relatively slow dissociation of candesartan, reassociation to the receptor, which is measurable in CHO-AT(1) cells, likely contributes to its long-lasting blood pressure lowering effect in vivo...
  53. ncbi request reprint Interaction between the partially insurmountable antagonist valsartan and human recombinant angiotensin II type 1 receptors
    I Verheijen
    Department of Molecular and Biochemical Pharmacology, Free University of Brussels, Belgium
    Fundam Clin Pharmacol 14:577-85. 2000
    ..These kinetic data suggest that the insurmountable inhibition by valsartan is related to its relatively slow dissociation from the human AT1 receptors...
  54. ncbi request reprint Inhibition of angiotensin II-induced inositol phosphate production by triacid nonpeptide antagonists in CHO cells expressing human AT1 receptors
    P M Vanderheyden
    Department of Molecular and Biochemical Pharmacology, Institute of Molecular Biology and Biotechnology, Free University of Brussels, Sint Genesius Rode, Belgium
    Pharm Res 17:1482-8. 2000
    ..The aim of the present work is to describe the inhibitory properties of LY301875 and LY303336, two polysubstituted 4-aminoimidazole AT1 receptor antagonists, on CHO cells expressing human recombinant AT1 receptors...
  55. ncbi request reprint AT1 receptor antagonists
    I Verheijen
    Department of Molecular and Biochemical Pharmacology, Free University of Brussels VUB, 2 Pleinlaan, 1050 Brussels, Belgium
    Curr Med Chem Cardiovasc Hematol Agents 2:69-77. 2004
    ..This may contribute to their long lasting clinical effect. This paper also focuses on the influence of a number of methodological approaches used to study AT1 receptor antagonists on their observed in vitro receptor binding properties...
  56. pmc Translocation of the insulin-regulated aminopeptidase to the cell surface: detection by radioligand binding
    H Demaegdt
    Department of Molecular and Biochemical Pharmacology, Vrije Universiteit Brussel, Brussels, Belgium
    Br J Pharmacol 154:872-81. 2008
    ..A more widespread application of the method was demonstrated by the use of 3T3-L1 adipocytes...
  57. ncbi request reprint G protein-coupled receptors: a count of 1001 conformations
    G Vauquelin
    Department of Molecular and Biochemical Pharmacology, Institute for Molecular Biology and Biotechnology, Vrije Universiteit Brussel VUB, Pleinlaan 2, B 1050 Brussel, Belgium
    Fundam Clin Pharmacol 19:45-56. 2005
    ..g. other cellular proteins, lipids) allosteric modulators also affect ligand-GPCR interaction and receptor activation. These new developments in GPCR research could lead to the development of more selective therapeutic drugs...
  58. ncbi request reprint Lys(199) mutation of the human angiotensin type 1 receptor differentially affects the binding of surmountable and insurmountable non-peptide antagonists
    F L Fierens
    Department of Molecular and Biochemical Pharmacology, Free University of Brussels, Rode, B 1640, Belgium
    J Renin Angiotensin Aldosterone Syst 1:283-8. 2000
    ..His256 -->Ala substitution had only minor effects. This suggests that Lys199 is important for the tight binding of non-peptide antagonists...
  59. ncbi request reprint Formation of angiotensin-(1-7) from angiotensin II by the venom of Conus geographus
    Minh Tam Le
    Department of Molecular and Biochemical Pharmacology, Institute for Molecular Biology and Biotechnology, Free University of Brussels VUB, Paardenstraat 65, B 1640 Sint Genesius Rode, Belgium
    Regul Pept 105:101-8. 2002
    ..The molecular weight of the involved peptidases exceeds 50 kDa, as determined by gel chromatography and ultrafitration...
  60. doi request reprint Sartan-AT1 receptor interactions: in vitro evidence for insurmountable antagonism and inverse agonism
    I Van Liefde
    Department of Molecular and Biochemical Pharmacology, Institute for Molecular Biology and Biotechnology, Vrije Universiteit Brussel VUB, Brussel, Belgium
    Mol Cell Endocrinol 302:237-43. 2009
    ..This rather affects long-term, G protein-independent hypertrophic responses leading to cardiovascular remodelling...
  61. ncbi request reprint Subtypes of adrenergic and dopaminergic receptors in bovine cerebral blood vessels
    J De Keyser
    Department of Neurology, Akademisch Ziekenhuis, Vrije Universiteit Brussel, Belgium
    Neurosci Lett 85:272-6. 1988
    ..This suggests a functionally more important vasoconstrictor adrenergic control of the cerebral circulation in pial vessels of the convexity than in the arteries at the base of the brain...
  62. ncbi request reprint Cys2,7EtalphaCGRP is a potent agonist for CGRP1 receptors in SK-N-MC cells
    Christina Nodin
    Preclinical Research and Development, AstraZeneca Mölndal, 43183 Molndal, Sweden
    Biochem Pharmacol 69:1235-40. 2005
    ..Differences between the agonistic profile of this ligand in this and other experimental systems might be species--or even cell type--dependent...
  63. ncbi request reprint Inhibitory activity on binding of specific ligands to the human angiotensin II AT(1) and endothelin 1 ET(A) receptors: bioactive benzo[c]phenanthridine alkaloids from the root of Bocconia frutescens
    Catherina Caballero-George
    Department of Pharmaceutical Sciences, University of Antwerp, Antwerp, Belgium
    Planta Med 68:770-5. 2002
    ..Furthermore, the ability of these compounds to block AT(1) and/or ET(A) receptors may provide some justification for the traditional use of Bocconia frutescens L. to control hypertension...
  64. ncbi request reprint Cyclic insulin-regulated aminopeptidase (IRAP)/AT4 receptor ligands
    Andreas Axén
    Department of Medicinal Chemistry, Uppsala University, Box 574, SE 75123 Uppsala, Sweden
    J Pept Sci 12:705-13. 2006
    ..The cyclic constrained analogs allowed us to propose a tentative bioactive conformation of angiotensin IV and it seems that the peptide adopts an inverse gamma-turn at the C-terminal...
  65. ncbi request reprint Involvement of insulin-regulated aminopeptidase and/or aminopeptidase N in the angiotensin IV-induced effect on dopamine release in the striatum of the rat
    Bart Stragier
    Research Group Experimental Pharmacology, Department of Pharmaceutical Chemistry, Drug Analysis and Drug Information, Vrije Universiteit Brussel Laarbeeklaan 103 B 1090 Brussels, Belgium
    Brain Res 1131:97-105. 2007
    ..We therefore hypothesize that the effect of angiotensin IV on dopamine release in the striatum is mediated via activation of IRAP and/or AP-N, possibly acting as receptors for angiotensin IV...
  66. ncbi request reprint In vitro inhibition of [3H]-angiotensin II binding on the human AT1 receptor by proanthocyanidins from Guazuma ulmifolia bark
    Catherina Caballero-George
    Department of Pharmaceutical Sciences, University of Antwerp, Antwerp, Belgium
    Planta Med 68:1066-71. 2002
    ..Angiotensin II AT 1 receptor binding might be considered as a potentially interesting biological activity of proanthocyanidins contributing to the very broad spectrum of biological activities of the condensed tannins...
  67. ncbi request reprint Small potent ligands to the insulin-regulated aminopeptidase (IRAP)/AT(4) receptor
    Andreas Axén
    Department of Medicinal Chemistry, Uppsala University, Box 574, SE 751 23 Uppsala, Sweden
    J Pept Sci 13:434-44. 2007
    ..Furthermore, ligand 4 is degraded considerably more slowly in membrane preparations than angiotensin IV. Hence, it might constitute a suitable research tool for biological studies of the (IRAP)/AT(4) receptor...
  68. ncbi request reprint In vitro effect of sanguinarine alkaloid on binding of [3H]candesartan to the human angiotensin AT1 receptor
    Catherina Caballero-George
    Department of Pharmaceutical Sciences, University of Antwerp, Belgium
    Eur J Pharmacol 458:257-62. 2003
    ..The present findings indicate that sanguinarine interacts with the receptor in a slow, nearly irreversible and noncompetitive manner...
  69. ncbi request reprint Agonist induction and conformational selection during activation of a G-protein-coupled receptor
    Laszlo Hunyady
    Department of Physiology, Semmelweis University, Faculty of Medicine, Budapest, Hungary
    Trends Pharmacol Sci 24:81-6. 2003
    ..Because agonist binding also actively facilitates the conformational rearrangements leading to activation of other GPCRs we propose that agonist induction should be considered as a general mechanism of GPCR activation...
  70. doi request reprint Ligands to the (IRAP)/AT4 receptor encompassing a 4-hydroxydiphenylmethane scaffold replacing Tyr2
    Hanna Andersson
    Department of Medicinal Chemistry, Uppsala University, Box 574, SE 751 23 Uppsala, Sweden
    Bioorg Med Chem 16:6924-35. 2008
    ....
  71. pmc Expression, binding, and signaling properties of CRF2(a) receptors endogenously expressed in human retinoblastoma Y79 cells: passage-dependent regulation of functional receptors
    Eric Gutknecht
    CNS Research, Johnson and Johnson Research and Development, Beerse, Belgium
    J Neurochem 104:926-36. 2008
    ..These data demonstrate that Y79 cells express functional CRF1 and CRF2a receptors and that the CRF2(a) receptor protein is up-regulated during prolonged culture...