calcium channel agonists


Summary: Agents that increase calcium influx into calcium channels of excitable tissues. This causes vasoconstriction in VASCULAR SMOOTH MUSCLE and/or CARDIAC MUSCLE cells as well as stimulation of insulin release from pancreatic islets. Therefore, tissue-selective calcium agonists have the potential to combat cardiac failure and endocrinological disorders. They have been used primarily in experimental studies in cell and tissue culture.

Top Publications

  1. Duffy S, Cruse G, Brightling C, Bradding P. Adenosine closes the K+ channel KCa3.1 in human lung mast cells and inhibits their migration via the adenosine A2A receptor. Eur J Immunol. 2007;37:1653-62 pubmed
    ..1, providing a clearly defined mechanism by which adenosine inhibits HLMC migration and degranulation. A2A receptor agonists with channel-modulating function may be useful for the treatment of mast cell-mediated disease. ..
  2. Brunet S, Scheuer T, Klevit R, Catterall W. Modulation of CaV1.2 channels by Mg2+ acting at an EF-hand motif in the COOH-terminal domain. J Gen Physiol. 2005;126:311-23 pubmed
    ..2 channels, and reveal a potentially important role of Mg(i) binding to the COOH-terminal EF-hand in regulating Ca(2+) influx in physiological and pathophysiological states. ..
  3. Bannister R, Esteve E, Eltit J, Pessah I, Allen P, Lopez J, et al. A malignant hyperthermia-inducing mutation in RYR1 (R163C): consequent alterations in the functional properties of DHPR channels. J Gen Physiol. 2010;135:629-40 pubmed publisher
    ..Our present results indicate that mutations in RYR1 can alter DHPR activity and raise the possibility that this altered DHPR function may contribute to MH episodes...
  4. Esteve E, Eltit J, Bannister R, Liu K, Pessah I, Beam K, et al. A malignant hyperthermia-inducing mutation in RYR1 (R163C): alterations in Ca2+ entry, release, and retrograde signaling to the DHPR. J Gen Physiol. 2010;135:619-28 pubmed publisher
    ..These data suggest that conformational changes induced by the R163C MH mutation alter the retrograde signal that is sent from RYR1 to the DHPR, delaying the inactivation of the DHPR voltage sensor...
  5. Dehaven W, Smyth J, Boyles R, Bird G, Putney J. Complex actions of 2-aminoethyldiphenyl borate on store-operated calcium entry. J Biol Chem. 2008;283:19265-73 pubmed publisher
    ..These data reveal novel and complex actions of 2-APB effects on SOCE that can be attributed to effects on both STIM1 as well as Orai channel subunits. ..
  6. Armstrong G, Drapeau P. Calcium channel agonists protect against neuromuscular dysfunction in a genetic model of TDP-43 mutation in ALS. J Neurosci. 2013;33:1741-52 pubmed publisher
    ..all behavioral and cellular features were stabilized by chronic treatment with either of the L-type calcium channel agonists FPL 64176 or Bay K 8644...
  7. McDonough S, Mori Y, Bean B. FPL 64176 modification of Ca(V)1.2 L-type calcium channels: dissociation of effects on ionic current and gating current. Biophys J. 2005;88:211-23 pubmed
    ..Instead, FPL somehow affects the coupling of charge movement to opening and closing of the pore. An intriguing possibility is that the drug causes an inactivated state to become conducting without otherwise affecting gating transitions. ..
  8. Bell D, Butcher A, Berrow N, Page K, Brust P, Nesterova A, et al. Biophysical properties, pharmacology, and modulation of human, neuronal L-type (alpha(1D), Ca(V)1.3) voltage-dependent calcium currents. J Neurophysiol. 2001;85:816-27 pubmed
  9. Mark Duffy S, Berger P, Cruse G, Yang W, Bolton S, Bradding P. The K+ channel iKCA1 potentiates Ca2+ influx and degranulation in human lung mast cells. J Allergy Clin Immunol. 2004;114:66-72 pubmed
    ..Opening of iKCA1 enhances IgE-dependent Ca2+ influx and histamine release in HLMCs. Inhibition of iKCA1 may provide a novel approach to the treatment of mast cell-mediated disease. ..

More Information


  1. Beer T, Myrthue A. Calcitriol in cancer treatment: from the lab to the clinic. Mol Cancer Ther. 2004;3:373-81 pubmed
    ..Further work is needed to elucidate the molecular mechanisms of antineoplastic activity and optimal clinical applications of calcitriol in cancer. ..
  2. Morris S, Nerou E, Riley A, Potter B, Taylor C. Determinants of adenophostin A binding to inositol trisphosphate receptors. Biochem J. 2002;367:113-20 pubmed
    ..In addition we suggest that C-terminal residues, which impede access of IP(3), may selectively interact with adenophostin A to allow it unhindered access to the IP(3)-binding domain. ..
  3. Wasserstrom J, Wasserstrom L, Lokuta A, Kelly J, Reddy S, Frank A. Activation of cardiac ryanodine receptors by the calcium channel agonist FPL-64176. Am J Physiol Heart Circ Physiol. 2002;283:H331-8 pubmed
    ..006 in 150 microM FPL (no significant difference). These results suggest that, in addition to its ability to activate the L-type Ca(2+) channels, FPL activates cardiac RyR2 primarily by reducing the Ca(2+) sensitivity of inactivation. ..
  4. Mitra P, Slaughter M. Calcium-induced transitions between the spontaneous miniature outward and the transient outward currents in retinal amacrine cells. J Gen Physiol. 2002;119:373-88 pubmed
    ..Based on their characteristics, SMOCs in retinal neurons may function as synaptic noise suppressors at quiescent glutamatergic synapses...
  5. Mitra P, Slaughter M. Mechanism of generation of spontaneous miniature outward currents (SMOCs) in retinal amacrine cells. J Gen Physiol. 2002;119:355-72 pubmed
    ..This amplified Ca(2+) signal in turn activates BK channels in a discontinuous fashion, resulting in randomly occurring SMOCs...
  6. Fan J, Palade P. Effects of FPL 64176 on Ca transients in voltage-clamped rat ventricular myocytes. Br J Pharmacol. 2002;135:1495-504 pubmed
    ..5. Abolition by FPL 64176 of the increased gain normally seen at negative potentials rendered it impossible to confirm or refute the claim that a single Ca ion suffices to activate ryanodine receptors. ..
  7. Parekh A, Riley A, Potter B. Adenophostin A and ribophostin, but not inositol 1,4,5-trisphosphate or manno-adenophostin, activate the Ca2+ release-activated Ca2+ current, I(CRAC), in weak intracellular Ca2+ buffer. Biochem J. 2002;361:133-41 pubmed
  8. Correa V, Riley A, Shuto S, Horne G, Nerou E, Marwood R, et al. Structural determinants of adenophostin A activity at inositol trisphosphate receptors. Mol Pharmacol. 2001;59:1206-15 pubmed
    ..This is the first comprehensive analysis of all the key structural elements of adenophostin A, and it provides a working model for the design of related high-affinity ligands of InsP(3) receptors...
  9. Fujimori A, Sakai M, Yoshiya K, Shin J, Kim J, Inaba Y, et al. Bio-intact parathyroid hormone and intact parathyroid hormone in hemodialysis patients with secondary hyperparathyroidism receiving intravenous calcitriol therapy. Ther Apher Dial. 2004;8:474-9 pubmed
    ..Our limited data failed to demonstrate the superiority of BiPTH to iPTH. Therefore, further investigations would be necessary to examine the relationship between BiPTH and bone histomorphometry. ..
  10. Weissgerber P, Held B, Bloch W, Kaestner L, Chien K, Fleischmann B, et al. Reduced cardiac L-type Ca2+ current in Ca(V)beta2-/- embryos impairs cardiac development and contraction with secondary defects in vascular maturation. Circ Res. 2006;99:749-57 pubmed
    ..Taken together, these data strongly support the essential role of L-type Ca2+ channel activity in cardiomyocytes for normal heart development and function and that this is a prerequisite for proper maturation of the vasculature. ..
  11. Montaño L, Calixto E, Figueroa A, Flores Soto E, Carbajal V, Perusquía M. Relaxation of androgens on rat thoracic aorta: testosterone concentration dependent agonist/antagonist L-type Ca2+ channel activity, and 5beta-dihydrotestosterone restricted to L-type Ca2+ channel blockade. Endocrinology. 2008;149:2517-26 pubmed publisher
  12. Begum G, Dube A, Joshi P, Gupta P, Joshi N. Chlorin p6 preferentially localizes in endoplasmic reticulum and Golgi apparatus and inhibits Ca(2+) release from intracellular store. J Photochem Photobiol B. 2009;95:177-84 pubmed publisher
    ..These results suggest that the fluorescence imaging pattern of chlorin p6 could be useful in identifying the proliferating and differentiated population of cells in tumor tissue. ..
  13. Akiba Y, Watanabe C, Mizumori M, Kaunitz J. Luminal L-glutamate enhances duodenal mucosal defense mechanisms via multiple glutamate receptors in rats. Am J Physiol Gastrointest Liver Physiol. 2009;297:G781-91 pubmed publisher
    ..Luminal L-glutamate may activate multiple receptors and afferent nerves and locally enhance mucosal defenses to prevent subsequent injury attributable to acid exposure in the duodenum. ..
  14. Butakova S, Nozdrachev A. Effect of calcium-regulating hormones and calcium channel modulators on glucose consumption by muscle and adipose tissues in vivo and in vitro. Bull Exp Biol Med. 2009;148:171-4 pubmed
  15. Mackrill J. Ryanodine receptor calcium channels and their partners as drug targets. Biochem Pharmacol. 2010;79:1535-43 pubmed publisher
    ..This commentary examines the possibility of manipulating the expression and function of such proteins in order develop new drugs acting on RyR channel complexes. ..
  16. Tian C, Shao C, Fenster D, Mixan M, Romberger D, Toews M, et al. Chloroform extract of hog barn dust modulates skeletal muscle ryanodine receptor calcium-release channel (RyR1). J Appl Physiol (1985). 2010;109:830-9 pubmed publisher
    ..Since persistent activation and/or closure of RyR1 results in skeletal muscle weakness, these new data suggest that HBD is responsible, at least in part, for the muscle ailment reported by hog confinement workers. ..
  17. Fernández Tenorio M, Porras González C, Castellano A, Lopez Barneo J, Ureña J. Tonic arterial contraction mediated by L-type Ca2+ channels requires sustained Ca2+ influx, G protein-associated Ca2+ release, and RhoA/ROCK activation. Eur J Pharmacol. 2012;697:88-96 pubmed publisher
    ..Because L-type Ca(2+) channels participate in numerous pathophysiological processes mediated by maintained arterial contraction, our data could help to optimize therapeutic treatment of arterial vasospasm. ..
  18. Diaz M. Application of Fourier linear spectral analyses to the characterization of smooth muscle contractile signals. J Biochem Biophys Methods. 2007;70:803-8 pubmed
  19. Kamata K, Satoh T, Matsumoto T, Noguchi E, Taguchi K, Kobayashi T, et al. Enhancement of methoxamine-induced contractile responses of rat ventricular muscle in streptozotocin-induced diabetes is associated with alpha1A adrenoceptor upregulation. Acta Physiol (Oxf). 2006;188:173-83 pubmed
  20. De Crescenzo V, Fogarty K, Zhuge R, Tuft R, Lifshitz L, Carmichael J, et al. Dihydropyridine receptors and type 1 ryanodine receptors constitute the molecular machinery for voltage-induced Ca2+ release in nerve terminals. J Neurosci. 2006;26:7565-74 pubmed
    ..VICaR may constitute a new link between neuronal activity, as signaled by depolarization, and a rise in intraterminal Ca2+. ..
  21. Noh A, Park H, Zheng T, Ha H, Yim M. L-type Ca(2+) channel agonist inhibits RANKL-induced osteoclast formation via NFATc1 down-regulation. Life Sci. 2011;89:159-64 pubmed publisher
    ..Our results provide a molecular understanding of the inhibitory effect of the L-type Ca(2+) channel agonist, BayK 8644, on osteoclastogenesis. ..
  22. Graydon C, Cho S, Li G, Kachar B, von Gersdorff H. Sharp Ca²? nanodomains beneath the ribbon promote highly synchronous multivesicular release at hair cell synapses. J Neurosci. 2011;31:16637-50 pubmed publisher
    ..We conclude that, by restricting the available presynaptic volume, the ribbon may be creating conditions for the synchronous release of a small cohort of docked vesicles. ..
  23. Chen S, Yue C, Yaari Y. A transitional period of Ca2+-dependent spike afterdepolarization and bursting in developing rat CA1 pyramidal cells. J Physiol. 2005;567:79-93 pubmed
    ..Thus, developing pyramidal neurones transitionally express not only distinctive synaptic properties, but also unique intrinsic firing patterns, that may contribute to the ongoing formation and refinement of synaptic connections. ..
  24. Reichel H. Current treatment options in secondary renal hyperparathyroidism. Nephrol Dial Transplant. 2006;21:23-8 pubmed
  25. Pelled D, Trajkovic Bodennec S, Lloyd Evans E, Sidransky E, Schiffmann R, Futerman A. Enhanced calcium release in the acute neuronopathic form of Gaucher disease. Neurobiol Dis. 2005;18:83-8 pubmed
    ..These findings suggest that defective calcium homeostasis may be a mechanism responsible for neuropathophysiology in acute neuronopathic Gaucher disease, and may potentially offer new therapeutic approaches for disease management. ..
  26. Di Luca M. [Treatment of secondary hyperparathyroidism in dialysis patients]. G Ital Nefrol. 2009;26 Suppl 49:S36-48 pubmed
  27. Borbouse L, Dick G, Asano S, Bender S, Dincer U, Payne G, et al. Impaired function of coronary BK(Ca) channels in metabolic syndrome. Am J Physiol Heart Circ Physiol. 2009;297:H1629-37 pubmed publisher
    ..Coronary vascular dysfunction in MetS is related to impaired BK(Ca) channel function and is accompanied by significant increases in L-type Ca(2+) channel-mediated coronary vasoconstriction. ..
  28. Zhang Y, Tuft R, Lifshitz L, Fogarty K, Singer J, Zou H. Caffeine-activated large-conductance plasma membrane cation channels in cardiac myocytes: characteristics and significance. Am J Physiol Heart Circ Physiol. 2007;293:H2448-61 pubmed
    ..Moreover, these events in cardiac cells suggest a possible additional mechanism by which caffeine and theophylline contribute to the generation of cardiac arrhythmias. ..
  29. Jorquera G, Altamirano F, Contreras Ferrat A, Almarza G, Buvinic S, Jacquemond V, et al. Cav1.1 controls frequency-dependent events regulating adult skeletal muscle plasticity. J Cell Sci. 2013;126:1189-98 pubmed publisher
  30. Sarkozi S, Komáromi I, Jona I, Almassy J. Lanthanides Report Calcium Sensor in the Vestibule of Ryanodine Receptor. Biophys J. 2017;112:2127-2137 pubmed publisher
    ..These results suggest that maurocalcine mechanically prevented Ca2+ from dissociating from its binding site and support our vestibular Ca2+ sensor-model further. ..
  31. Santonastasi M, Wehrens X. Ryanodine receptors as pharmacological targets for heart disease. Acta Pharmacol Sin. 2007;28:937-44 pubmed
    ..Pharmacological agents known to modulate RyR in the heart, and their potential application towards the treatment of heart disease are discussed in this review. ..
  32. Xu M, Wu Y, Liu S, Li Q, He R. Electrophysiological effects of hydrogen sulfide on human atrial fibers. Chin Med J (Engl). 2011;124:3455-9 pubmed
    ..Endogenous H(2)S may be generated by CSE and act as an important regulator of electrophysiological properties in human atrial fibers. ..
  33. Kashihara T, Nakada T, Shimojo H, Horiuchi Hirose M, Gomi S, Shibazaki T, et al. Chronic receptor-mediated activation of Gi/o proteins alters basal t-tubular and sarcolemmal L-type Ca²? channel activity through phosphatases in heart failure. Am J Physiol Heart Circ Physiol. 2012;302:H1645-54 pubmed publisher
    ..These results indicate that chronic receptor-mediated activation of G(i/o) in vivo decreases basal TT LTCC activity by activating PP2A and increases basal SS LTCC activity by inhibiting PP1 without modulating PKA in heart failure. ..
  34. Petrie M, Harrell T, Schwartz G, Sane D. Production of plasminogen activator inhibitor-1 (PAI-1) by endothelial cells: differential responses to calcitriol and paricalcitol. J Thromb Haemost. 2004;2:2266-7 pubmed
  35. Tarr T, Malick W, Liang M, Valdomir G, Frasso M, Lacomis D, et al. Evaluation of a novel calcium channel agonist for therapeutic potential in Lambert-Eaton myasthenic syndrome. J Neurosci. 2013;33:10559-67 pubmed publisher
    ..This new Ca(2+) channel agonist has potential as a lead compound in the development of new therapeutic approaches to a variety of disorders that result in neuromuscular weakness. ..
  36. Namkung W, Yao Z, Finkbeiner W, Verkman A. Small-molecule activators of TMEM16A, a calcium-activated chloride channel, stimulate epithelial chloride secretion and intestinal contraction. FASEB J. 2011;25:4048-62 pubmed publisher
    ..Small-molecule, TMEM16A-targeted activators may be useful for drug therapy of cystic fibrosis, dry mouth, and gastrointestinal hypomotility disorders, and for pharmacological dissection of TMEM16A function...
  37. Cui S, Cui X, Zhang J, Wang Z, Yu B, Sheng Z, et al. Ca²+ modulation in dorsal raphe plays an important role in NREM and REM sleep regulation during pentobarbital hypnosis. Brain Res. 2011;1403:12-8 pubmed publisher
    ..These results suggested that the suppression of Ca(2+) function in DRN could increase NREM sleep including SWS, and the elevation of Ca(2+) function could reduce both NREM and REM sleep in pentobarbital treated rats. ..
  38. Stewart L, Weigel N. Role of insulin-like growth factor binding proteins in 1alpha,25-dihydroxyvitamin D(3)-induced growth inhibition of human prostate cancer cells. Prostate. 2005;64:9-19 pubmed
    ..Our studies indicate 1,25D-induced up-regulation of IGFBP-3 is not required for the growth inhibitory effects of 1,25D in prostate cancer cells grown in serum-containing media. ..
  39. Lundqvist J, Norlin M, Wikvall K. 1alpha,25-Dihydroxyvitamin D3 affects hormone production and expression of steroidogenic enzymes in human adrenocortical NCI-H295R cells. Biochim Biophys Acta. 2010;1801:1056-62 pubmed publisher
  40. Winer K, Sinaii N, Reynolds J, Peterson D, Dowdy K, Cutler G. Long-term treatment of 12 children with chronic hypoparathyroidism: a randomized trial comparing synthetic human parathyroid hormone 1-34 versus calcitriol and calcium. J Clin Endocrinol Metab. 2010;95:2680-8 pubmed publisher
    ..Additionally, PTH 1-34 treatment allowed normal skeletal development because there were no differences in bone mineral accrual, linear growth, or weight gain between the two treatment arms over the 3-yr study period. ..
  41. Salpeter S, Klochendler A, Weinberg Corem N, Porat S, Granot Z, Shapiro A, et al. Glucose regulates cyclin D2 expression in quiescent and replicating pancreatic ?-cells through glycolysis and calcium channels. Endocrinology. 2011;152:2589-98 pubmed publisher
    ..These data challenge the standard model for regulation of cyclin D2 during the cell division cycle and suggest cyclin D2 as a molecular link between glucose levels and ?-cell replication. ..
  42. Niramitmahapanya S, Sunthornthepvarakul T, Deerochanawong C, Sarinnapakorn V, Athipan P. Role of loading calcitriol to control hypocalcemia after parathyroidectomy in chronic kidney disease. J Med Assoc Thai. 2011;94:295-302 pubmed
    ..75-1.5 mcg/day) (p = 0.001). Loading calcitriol regimen reduced hypocalcemic morbidity in postoperative parathyroidectomy in patients with chronic kidney disease. ..
  43. Courbebaisse M, Souberbielle J. [Phosphocalcic metabolism: regulation and explorations]. Nephrol Ther. 2011;7:118-38 pubmed publisher
    ..Hence, the understanding of physiopathological mechanisms has been improved by newly identified genetic disorders responsible for phophocalcic homeostasis disturbances. ..
  44. Rossi A, Sureshan K, Riley A, Potter V, Taylor C. Selective determinants of inositol 1,4,5-trisphosphate and adenophostin A interactions with type 1 inositol 1,4,5-trisphosphate receptors. Br J Pharmacol. 2010;161:1070-85 pubmed publisher
    ..The 2'-phosphate of AdA is not a major determinant of its high affinity. R504 in the receptor, most likely via a cation-? interaction, contributes specifically to AdA binding. ..
  45. Garaliene V, Barsys V, Jakuska P, Krauze A, Duburs G. Effects of calcium antagonists and agonists on isolated human v. saphena magna used for coronary artery bypass grafting and guinea pig's papillary muscle. Arzneimittelforschung. 2011;61:386-92 pubmed publisher
    ..These responses point to a different mechanism of action underlying both calcium antagonist and agonist effects even though their action ultimately resulted in vasodilatation. ..
  46. Tencerová B, Zahradnikova A, Gaburjakova J, Gaburjakova M. Luminal Ca2+ controls activation of the cardiac ryanodine receptor by ATP. J Gen Physiol. 2012;140:93-108 pubmed publisher
  47. Tsagareli M, Tsiklauri N, Zanotto K, Carstens M, Klein A, Sawyer C, et al. Behavioral evidence of thermal hyperalgesia and mechanical allodynia induced by intradermal cinnamaldehyde in rats. Neurosci Lett. 2010;473:233-6 pubmed publisher
    ..The data are consistent with roles for TRPA1 in thermal (hot and cold) hyperalgesia and mechanical allodynia. ..
  48. Duffy S, Cruse G, Cockerill S, Brightling C, Bradding P. Engagement of the EP2 prostanoid receptor closes the K+ channel KCa3.1 in human lung mast cells and attenuates their migration. Eur J Immunol. 2008;38:2548-56 pubmed publisher
    ..1 in HLMC and attenuates both chemokine- and PGE(2)-dependent HLMC migration. EP(2) receptor agonists with K(Ca)3.1 modulating function may be useful for the treatment of mast cell-mediated disease. ..
  49. Beyer T, Solorzano C, Prinz R, Babu A, Nilubol N, Patel S. Oral vitamin D supplementation reduces the incidence of eucalcemic PTH elevation after surgery for primary hyperparathyroidism. Surgery. 2007;141:777-83 pubmed
    ..04) and at 7 to 12 months (22% vs 83%; P = .04). Vitamin D supplementation following parathyroidectomy for primary hyperparathyroidism reduces the incidence of postoperative eucalcemic PTH elevation. ..
  50. Clark J, Symington S. Neurotoxic implications of the agonistic action of CS-syndrome pyrethroids on the N-type Ca(v)2.2 calcium channel. Pest Manag Sci. 2008;64:628-38 pubmed publisher
    ..The present findings may provide a partial explanation for the different toxic syndromes produced by these structurally distinct pyrethroids. ..
  51. Zhang H, Liu S, Wang X, Zhang C. [Protective effect of calcium channel agonist BayK8644 on lungs against ischemia-reperfusion injury in rabbits]. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2010;35:1091-8 pubmed publisher
    ..05). Appropriate BayK8644 preconditioning can induce transient Ca²+ influx, and elicit strong protection against the lung ischemia-reperfusion injury, which can simulate the endogenous protective effect of ischemic preconditioning. ..
  52. Viola H, Davies S, Filipovska A, Hool L. L-type Ca(2+) channel contributes to alterations in mitochondrial calcium handling in the mdx ventricular myocyte. Am J Physiol Heart Circ Physiol. 2013;304:H767-75 pubmed publisher
    ..This perturbation may contribute to the development of cardiomyopathy. ..
  53. Hayashi S, Nakamura E, Endo T, Kubo Y, Takeuchi K. Impairment by activation of TRPA1 of gastric epithelial restitution in a wound model using RGM1 cell monolayer. Inflammopharmacology. 2007;15:218-22 pubmed