leucine 2 alanine enkephalin


Summary: A delta-selective opioid (ANALGESICS, OPIOID). It can cause transient depression of mean arterial blood pressure and heart rate.

Top Publications

  1. Borlongan C, Su T, Wang Y. Delta opioid peptide augments functional effects and intrastriatal graft survival of rat fetal ventral mesencephalic cells. Cell Transplant. 2001;10:53-8 pubmed
    ..These results suggest that DADLE should be considered as an adjunctive agent for neural transplantation therapy in Parkinson's disease. ..
  2. Borlongan C, Wang Y, SU T. Delta opioid peptide (D-Ala 2, D-Leu 5) enkephalin: linking hibernation and neuroprotection. Front Biosci. 2004;9:3392-8 pubmed
    ..These results taken together suggest that DADLE stands as a novel therapeutic agent. In this review paper, we present laboratory evidence supporting the use of DADLE for protection of peripheral and central nervous system. ..
  3. Chao D, Donnelly D, Feng Y, Bazzy Asaad A, Xia Y. Cortical delta-opioid receptors potentiate K+ homeostasis during anoxia and oxygen-glucose deprivation. J Cereb Blood Flow Metab. 2007;27:356-68 pubmed
    ..We conclude that an important aspect of DOR-mediated neuroprotection is its early action against derangement of K(+) homeostasis during anoxia or ischemia. ..
  4. Chao D, Bazzy Asaad A, Balboni G, Xia Y. delta-, but not mu-, opioid receptor stabilizes K(+) homeostasis by reducing Ca(2+) influx in the cortex during acute hypoxia. J Cell Physiol. 2007;212:60-7 pubmed
    ..These data suggest that DOR, but not MOR, activation is protective against anoxic K(+) derangement in the cortex, at least partially via an inhibition of hypoxia-induced increase in Ca(2+) entry-BK channel activity. ..
  5. Su D, Wang Z, Zheng Y, Zhao Y, Wang X. Dose-dependent neuroprotection of delta opioid peptide [D-Ala2, D-Leu5] enkephalin in neuronal death and retarded behavior induced by forebrain ischemia in rats. Neurosci Lett. 2007;423:113-7 pubmed
  6. Borlongan C, Hayashi T, Oeltgen P, SU T, Wang Y. Hibernation-like state induced by an opioid peptide protects against experimental stroke. BMC Biol. 2009;7:31 pubmed publisher
    ..The present study demonstrates that delta opioids are crucially involved in stroke, suggesting that the opioid system is important in the study of brain injury and protection. ..
  7. Zhang J, Qian H, Zhao P, Hong S, Xia Y. Rapid hypoxia preconditioning protects cortical neurons from glutamate toxicity through delta-opioid receptor. Stroke. 2006;37:1094-9 pubmed
    ..DOR is involved in neuroprotection induced by rapid HPC in cortical neurons. ..
  8. Iwata M, Inoue S, Kawaguchi M, Nakamura M, Konishi N, Furuya H. Effects of delta-opioid receptor stimulation and inhibition on hippocampal survival in a rat model of forebrain ischaemia. Br J Anaesth. 2007;99:538-46 pubmed
    ..These data suggest that DOP activation with endogenous DOP ligand may be involved in self-protecting ischaemia-sensitive regions of the brain. ..
  9. Orlova E, Komarevtseva I. [Effect of dalarginum on the level of nitric oxide stable metabolites in rat kidneys during apoptosis activation]. Ukr Biokhim Zh (1999). 2002;74:131-4 pubmed
    ..Administration of dalarginum resulted in the significant decrease of NO--nitrite- and nitrate anions stable metabolites content, the latter is capable to be one of the mechanisms of the preparation antiapoptotic effect. ..

More Information

Publications105 found, 100 shown here

  1. Portoghese P, Law P, Loh H. Effect of opioid receptor ligands on the mu-S196A knock-in and mu knockout mouse vas deferens. Eur J Pharmacol. 2003;478:207-10 pubmed
    ..Identical IC50 values of DADLE obtained on the wild-type, S196A knock-in, and mu-opioid receptor knockout preparations support the absence of mu-delta heterodimers in the mouse vas deferens. ..
  2. Jiang Q, Sheldon R, Porreca F. Opioid modulation of basal intestinal fluid transport in the mouse: actions at central, but not intestinal, sites. J Pharmacol Exp Ther. 1990;253:784-90 pubmed
    ..p. administration. The effects of i.c.v. or i.p. morphine were blocked by i.c.v. SR 58002C, a quaternary opioid antagonist which had no effects alone.(ABSTRACT TRUNCATED AT 250 WORDS) ..
  3. Lebed ko O, Timoshin S. Correction of L-NAME-induced disturbances in DNA synthesis and free radical oxidation in respiratory organs of newborn albino rats with dalargin. Bull Exp Biol Med. 2002;133:433-5 pubmed
    ..Correcting activity of dalargin is associated with its antiradical and antioxidant properties. ..
  4. Yamanouchi K, Yanaga K, Okudaira S, Eguchi S, Furui J, Kanematsu T. [D-Ala2, D-Leu5] enkephalin (DADLE) protects liver against ischemia-reperfusion injury in the rat. J Surg Res. 2003;114:72-7 pubmed
    ..DADLE protects against I-R injury in hepatocytes, but not in the sinusoidal endothelial cells of the liver in rats. An anti-oxidative effect is suggested to be responsible for this effect. ..
  5. Johnson S, Kinney M, Wiegel L. Inhibitory and excitatory effects of micro-, delta-, and kappa-opioid receptor activation on breathing in awake turtles, Trachemys scripta. Am J Physiol Regul Integr Comp Physiol. 2008;295:R1599-612 pubmed publisher
    ..0 h after agonist injections. These results show that MOR and DOR activation causes respiratory depression as a result of decreased breathing frequency, whereas Vt is increased after KOR activation. ..
  6. Lane C, Elde R, Loh H, Lee N. Regulation of an opioid-binding protein in NG108-15 cells parallels regulation of delta-opioid receptors. Proc Natl Acad Sci U S A. 1992;89:11234-8 pubmed
    ..Taken together, these results strongly suggest that OBCAM has a role in opioid-receptor function in NG108-15 cells. ..
  7. Solínová V, Kašička V, Barth T, Hauzerová L, Fanali S. Analysis and separation of enkephalin and dalargin analogues and fragments by capillary zone electrophoresis. J Chromatogr A. 2005;1081:9-18 pubmed
    ..In addition, the selected characteristics of the UV-absorption detector (noise, signal to noise ratio, sensitivity, and limits of detection and quantification) were determined. ..
  8. Zhivotova E, Fleishman M, Sazonova E, Lebed ko O, Timoshin S. Gastroprotective effect of dalargin in gastropathy due to treatment with nonsteroid antiinflammatory drugs. Bull Exp Biol Med. 2009;147:441-3 pubmed
    ..Administration of [Dala]2-leu-enkephalin did not improve the state of the gastric mucosa. ..
  9. Förster K, Richter H, Alexeyev M, Rosskopf D, Felix S, Krieg T. Inhibition of glycogen synthase kinase 3beta prevents peroxide-induced collapse of mitochondrial membrane potential in rat ventricular myocytes. Clin Exp Pharmacol Physiol. 2010;37:684-8 pubmed publisher
    ..5. These experiments confirm that inhibition of GSK3 beta protects the myocytes, but also that the preconditioning mimetic DADLE loses its protective effect when a constitutively active GSK3 beta is present. ..
  10. Benyhe S, Varga E, Borsodi A, Wollemann M. The occurrence of different kappa opioid receptors (K1 and K2) in frog (Rana esculenta) brain membranes. Acta Physiol Hung. 1990;76:291-4 pubmed
    ..The kappa 2 subtype in frog brain resembles more to the mu subtype than to the delta subtype of opioid receptors, but it differs from the mu subtype in displaying low affinity toward beta-endorphin and DAGO. ..
  11. Zhao P, Kuai J, Gao J, Sun L, Wang Y, Yao L. Delta opioid receptor agonist attenuates lipopolysaccharide-induced myocardial injury by regulating autophagy. Biochem Biophys Res Commun. 2017;492:140-146 pubmed publisher
    ..DADLE could improve the survival and protect myocardial dysfunction in mice with LPS-induced endotoxemia. This effect was related to the increase of autophagy. ..
  12. Sánchez Blázquez P, Garzon J. Evaluation of delta receptor mediation of supraspinal opioid analgesia by in vivo protection against the beta-funaltrexamine antagonist effect. Eur J Pharmacol. 1989;159:9-23 pubmed
    ..These results suggest that delta ligands, after binding to delta receptors, also need to act upon mu receptors to produce high levels of supraspinal analgesia in the tail immersion test. ..
  13. Rossi F, Quirico N, Carillo C. Ethanol retains its ability to modify endogenous opiate system in aged rats. Riv Neurol. 1988;58:127-30 pubmed
    ..In contrast the affinity of mu receptors is decreased. These changes are qualitatively and quantitatively similar in young and old rats. ..
  14. Fu D, Liu H, Li S, Chen L, Yao J. Antioxidative and Antiapoptotic Effects of Delta-Opioid Peptide [D-Ala2, D-Leu5] Enkephalin on Spinal Cord Ischemia-Reperfusion Injury in Rabbits. Front Neurosci. 2017;11:603 pubmed publisher
    ..b>Conclusions: The protective effects of DADLE at the dosage of 0.05 mg/kg may be related to its antioxidant and antiapoptosis properties in the rabbit model of spinal cord I/R injury...
  15. Bayguinov O, Sanders K. Regulation of neural responses in the canine pyloric sphincter by opioids. Br J Pharmacol. 1993;108:1024-30 pubmed
    ..Higher frequency stimulation (or longer durations of stimulation) appear to be necessary to release concentrations of opioids that are effective in modulating the amplitude of junction potentials. ..
  16. Lv M, Li B, Wang M, Meng F, Yu J, Guo F, et al. Activation of the PI3K-Akt pathway promotes neuroprotection of the δ-opioid receptor agonist against cerebral ischemia-reperfusion injury in rat models. Biomed Pharmacother. 2017;93:230-237 pubmed publisher
    ..These results indicate that activation of PI3K-Akt pathway promotes the neuroprotection of DADLE against cerebral I/R injury in a rat model by decreasing nerve cells apoptosis. ..
  17. Lee J, Liska M, Crowley M, Xu K, Acosta S, Borlongan C, et al. Multifaceted Effects of Delta Opioid Receptors and DADLE in Diseases of the Nervous System. Curr Drug Discov Technol. 2017;: pubmed publisher
    ..This review article discusses evidence supporting the potential of the delta-opioid family of receptors and its ligands in developing novel therapeutic strategies for stroke and other brain disorders...
  18. Tsai S, Lee C, Hayashi T, Freed W, SU T. Delta opioid peptide DADLE and naltrexone cause cell cycle arrest and differentiation in a CNS neural progenitor cell line. Synapse. 2010;64:267-73 pubmed publisher
    ..Results also suggest some potential utilization of DADLE and/or naltrexone in stem cell research. ..
  19. Lee J, Joshi S, Chan J, Wong Y. Differential coupling of mu-, delta-, and kappa-opioid receptors to G alpha16-mediated stimulation of phospholipase C. J Neurochem. 1998;70:2203-11 pubmed
    ..5- to almost 17-fold. These findings suggest that the promiscuous G alpha16 can in fact discriminate among different receptors and that such preferential interaction might in part be due to the abundance of receptors. ..
  20. Pencheva N, Pospisek J, Hauzerova L, Barth T, Milanov P. Activity profiles of dalargin and its analogues in mu-, delta- and kappa-opioid receptor selective bioassays. Br J Pharmacol. 1999;128:569-76 pubmed
    ..00053; KB=2.6 nM). The CONH2 terminus combined with the N-methylation of L-Phe4 increased the potency and selectivity of dalargin for mu-opioid receptors. ..
  21. Ouyang H, Vander Velde D, Borchardt R, Siahaan T. Synthesis and conformational analysis of a coumarinic acid-based cyclic prodrug of an opioid peptide with modified sensitivity to esterase-catalyzed bioconversion. J Pept Res. 2002;59:183-95 pubmed
  22. Jackman H, Massad M, Sekosan M, Tan F, Brovkovych V, Marcic B, et al. Angiotensin 1-9 and 1-7 release in human heart: role of cathepsin A. Hypertension. 2002;39:976-81 pubmed
    ..They probably induce conformational changes in the ACE/B(2) receptor complex via interaction with ACE. ..
  23. Molinari P, Ambrosio C, Riitano D, Sbraccia M, Grò M, Costa T. Promiscuous coupling at receptor-Galpha fusion proteins. The receptor of one covalent complex interacts with the alpha-subunit of another. J Biol Chem. 2003;278:15778-88 pubmed
    ..Moreover, the enhanced coupling efficiency commonly observed for fusion proteins is not due to the receptor tether, but to the transmembrane helix that anchors Galpha to the membrane. ..
  24. Lasukova T, Maslov L, Podoksenov Y, Podoksenov A, Platonov A, Ovchinnikov M, et al. Effect of opiate peptide dalargin and des-Tyr-dalargin on cardiac pump function during ischemia-reperfusion. Bull Exp Biol Med. 2004;137:27-30 pubmed
    ..We hypothesize that the influence of dalargin is related to activation of cardiac delta-opiate receptors, while the inotropic effect of des-Tyr-dalargin is mediated by other receptors. ..
  25. Camlica Y, Askin A, Comelekoglu U. Evidence for the involvement of an opioid system in sciatic nerve of Rana ridibunda. Neuropeptides. 2004;38:83-91 pubmed
    ..The depression of both peptides in action potential parameters was partially blocked by 1 x 10(-6) M naloxone. ..
  26. Maslov L, Lishmanov I, Barzakh E, Maksimov I, Vorozgtsova I, Bukhovets I, et al. [Cardiovascular effects of D-ALA2, LEU5, ARG6-enkephalin (dalargin) are mediated by peripheral mu-opioid receptor activation]. Eksp Klin Farmakol. 2008;71:21-8 pubmed
    ..Increase in the heart rate induced by dalargin had a reflex nature. Direct action of dalargin on the heart was accompanied by a decrease in the heart rate and a delay in the cardiac conductance in the atrioventricular junction region. ..
  27. Garzon J, Defelipe J, Rodriguez J, DeAntonio I, Garcia Espana A, Sánchez Blázquez P. Transport of CSF antibodies to Galpha subunits across neural membranes requires binding to the target protein and protein kinase C activity. Brain Res Mol Brain Res. 1999;65:151-66 pubmed
    ..These results indicate that IgGs delivered into the CSF show a saturable binding to Galpha subunits that translocate to the external side of the neural membrane before being internalized by a PKCbeta1-dependent mechanism. ..
  28. Kreuter J, Ramge P, Petrov V, Hamm S, Gelperina S, Engelhardt B, et al. Direct evidence that polysorbate-80-coated poly(butylcyanoacrylate) nanoparticles deliver drugs to the CNS via specific mechanisms requiring prior binding of drug to the nanoparticles. Pharm Res. 2003;20:409-16 pubmed
  29. Yushkov B, Chereshnev V, Tyumentseva N, Artashyan O, Kuz min A. System of hemopoiesis and morphogenesis. Bull Exp Biol Med. 2005;140:627-30 pubmed
    ..The morphogenetic effect of transplantation depended on the state of damaged tissue and was determined by not only hemopoietic stem cells, but also lymphocytes, macrophages, and mast cells. ..
  30. Sirohi S, Aldrich J, Walker B. Species differences in the effects of the ?-opioid receptor antagonist zyklophin. Alcohol. 2016;51:43-9 pubmed publisher
    ..These results identify species differences in zyklophin efficacy that, given the rising interest in the development of short-duration KOR antagonists, should provide valuable information for therapeutic development efforts. ..
  31. Gramsch C, Schulz R, Kosin S, Herz A. Monoclonal anti-idiotypic antibodies to opioid receptors. J Biol Chem. 1988;263:5853-9 pubmed
    ..Our findings demonstrate the successful generation of monoclonal antibodies interacting with membrane-bound and solubilized opioid receptors of the mu- and delta-type. ..
  32. Bolling S, Tramontini N, Kilgore K, Su T, Oeltgen P, Harlow H. Use of "natural" hibernation induction triggers for myocardial protection. Ann Thorac Surg. 1997;64:623-7 pubmed
    ..quot;Natural" HIT protection is superior to standard cardioplegia alone and may have clinical application. ..
  33. Gyires K, Mullner K, Ronai A. Activation of central opioid receptors may induce gastric mucosal defence in the rat. J Physiol Paris. 2001;95:189-96 pubmed
  34. Chen W, Yang J, Andersen R, Nielsen L, Borchardt R. Evaluation of the permeation characteristics of a model opioid peptide, H-Tyr-D-Ala-Gly-Phe-D-Leu-OH (DADLE), and its cyclic prodrugs across the blood-brain barrier using an in situ perfused rat brain model. J Pharmacol Exp Ther. 2002;303:849-57 pubmed
    ..1% from AOA-DADLE, 0.6% from CA-DADLE, and 0.2% from OMCA-DADLE), which was consistent with the in vitro bioconversion rates determined previously in rat brain homogenates. ..
  35. Wang J, Zhao M, Huang F, Tang J, Yuan Y. Mu-opioid receptor in the nucleus submedius: involvement in opioid-induced inhibition of mirror-image allodynia in a rat model of neuropathic pain. Neurochem Res. 2008;33:2134-41 pubmed publisher
    ..These results suggest that Sm opioid receptor signaling is involved in inhibition of mirror-image allodynia; this effect is mediated by mu- (but not delta- and kappa-) opioid receptors in the rat model of neuropathic pain. ..
  36. Szabo B, Hedler L, Schurr C, Starke K. Peripheral sympatho-inhibitory cardiovascular effects of opioid peptides in anaesthetized rabbits. Br J Pharmacol. 1988;94:781-8 pubmed
    ..The effects of DADLE are more complex and may involve both central and peripheral components. ..
  37. Kampa M, Margioris A, Hatzoglou A, Dermitzaki I, Denizot A, Henry J, et al. Kappa1-opioid binding sites are the dominant opioid binding sites in surgical specimens of human pheochromocytomas and in a human pheochromocytoma (KAT45) cell line. Eur J Pharmacol. 1999;364:255-62 pubmed
    ..We found no correlation between the type of the predominant catecholamine produced and the opioid binding profile of each tumor suggesting that this hypothesis may not be valid. ..
  38. Coles J, Sigg D, Iaizzo P. Role of kappa-opioid receptor activation in pharmacological preconditioning of swine. Am J Physiol Heart Circ Physiol. 2003;284:H2091-9 pubmed
    ..kappa-Opioid receptor blockade with DADLE or pentazocine preconditioning alleviated proarrhythmic effects. These results suggest that kappa-opioid receptor activation during pharmacological preconditioning is proarrhythmic in swine. ..
  39. Ke S, Dian san S, Xiang rui W. Delta opioid agonist [D-Ala2, D-Leu5] enkephalin (DADLE) reduced oxygen-glucose deprivation caused neuronal injury through the MAPK pathway. Brain Res. 2009;1292:100-6 pubmed publisher
    ..Neither DADLE nor Naltrindole had any appreciable effect on phosphorylation of JNK. One of the protective mechanisms of DADLE on OGD neurons may be due to the dynamic balance between the activation of ERK and the p38. ..
  40. Adler B, Goodman R, Pasternak G. Quantitative autoradiographic distribution of meptazinol-sensitive binding sites in rat brain. Cell Mol Neurobiol. 1988;8:471-6 pubmed
    ..The correlation between the inhibition of [3H]DAGO binding by meptazinol and that by DADL was high (r = 0.83), consistent with the binding of meptazinol to mu 1 sites. ..
  41. Menzebach A, Hirsch J, Hempelmann G, Welters I. Effects of endogenous and synthetic opioid peptides on neutrophil function in vitro. Br J Anaesth. 2003;91:546-50 pubmed
    ..This study may contribute to a better understanding of neuroimmune interaction. ..
  42. Teng L, Zhao J, Wang F, Ma L, Pei G. A GPCR/secretase complex regulates beta- and gamma-secretase specificity for Abeta production and contributes to AD pathogenesis. Cell Res. 2010;20:138-53 pubmed publisher
  43. Porreca F, Lopresti D, Ward S. Opioid agonist affinity in the guinea-pig ileum and mouse vas deferens. Eur J Pharmacol. 1990;179:129-39 pubmed
  44. Liebmann C, Schrader U, Brantl V. Opioid receptor affinities of the blood-derived tetrapeptides hemorphin and cytochrophin. Eur J Pharmacol. 1989;166:523-6 pubmed
    ..However, they showed markedly higher affinities at kappa-opioid binding sites when compared to the beta-casomorphins. These blood-derived peptides could be involved in blood pressure regulation. ..
  45. Borea P, Bertelli G, Gilli G. Temperature dependence of the binding of mu, delta and kappa agonists to the opiate receptors in guinea-pig brain. Eur J Pharmacol. 1988;146:247-52 pubmed
    ..The present results do not agree with the hypothesis that agonist binding is associated with very small or negative delta S0 (in opposition to antagonists) in view of the information transfer involved (the biological effect). ..
  46. Hatzoglou A, Gravanis A, Margioris A, Zoumakis E, Castanas E. Identification and characterization of opioid-binding sites present in the Ishikawa human endometrial adenocarcinoma cell line. J Clin Endocrinol Metab. 1995;80:418-23 pubmed
    ..e. in epithelial cells. The coexistence of opioid sites and their endogenous ligands in the Ishikawa cell line makes these cells a good model for the study of autocrine/paracrine interactions of opioids in nonneural tissues. ..
  47. Formenti A, Arrigoni E, Mancia M. Two distinct modulatory effects on calcium channels in adult rat sensory neurons. Biophys J. 1993;64:1029-37 pubmed
    ..GTP-'y-S (100 ,uM) intracellularly perfused mimicked both the modulatory effects. The two modulations may have different functions in processing nociceptive inputs. ..
  48. Campos M, Casalino Matsuda S, Linares J, Goldraij A. Opioid effects on glucose and eicosanoid metabolism in isolated uterus of ovariectomized and non-ovariectomized restricted diet rats. Prostaglandins Leukot Essent Fatty Acids. 2001;65:117-22 pubmed
    ..These likely originate in other tissues, and so prevent us from seeing the morphine effect. ..
  49. Ouyang H, Tang F, Siahaan T, Borchardt R. A modified coumarinic acid-based cyclic prodrug of an opioid peptide: its enzymatic and chemical stability and cell permeation characteristics. Pharm Res. 2002;19:794-801 pubmed
    ..However, the prodrug was a good substrate for both P-gp and MRP2 suggesting that its permeation across intestinal mucosa and blood-brain barrier would be significantly restricted. ..
  50. Maslov L, Barzakh E, Platonov A, Minin S, Ovchinnikov M. Chronotropic effect of D-Ala2,Leu5,Arg6-enkephalin (dalargin) is associated with activation of peripheral kappa-opioid receptors. Bull Exp Biol Med. 2005;140:682-6 pubmed
    ..Agonists and antagonists of delta-opioid receptors caused persistent bradycardia. We hypothesized that selective delta-opioid antagonists exhibit properties of partial delta-receptor agonists. ..
  51. Smith C, Waldron C, Brook N. Opioid receptors in the mouse ileum. Arch Int Pharmacodyn Ther. 1988;291:122-31 pubmed
    ..1 microM) and delta (15.6 microM) receptors. A comparison has been made between the relative proportions of opioid receptor subtypes found in the mouse ileum and those found in the mouse vas deferens and guinea-pig ileum. ..
  52. Olivier J, Fenart L, Chauvet R, Pariat C, Cecchelli R, Couet W. Indirect evidence that drug brain targeting using polysorbate 80-coated polybutylcyanoacrylate nanoparticles is related to toxicity. Pharm Res. 1999;16:1836-42 pubmed
    ..A non specific permeabilization of the BBB, probably related to the toxicity of the carrier, may account for the CNS penetration of dalargin associated with PBCA NP and polysorbate 80. ..
  53. Nano J, Fournel S, Rampal P. Characterization of delta-opioid receptors and effect of enkephalins on IRD 98 rat epithelial intestinal cell line. Pflugers Arch. 2000;439:547-54 pubmed
    ..Enkephalins can regulate intestinal secretion by acting directly on enterocytes: they thus have an antidiarrheal role, especially in the presence of an enkephalinase inhibitor. ..
  54. Stefani A, Spadoni F, Giacomini P, Lavaroni F, Bernardi G. The activation of mu opioid receptors promotes a small modulation of calcium currents in rat pallidal neurons. Brain Res. 2001;897:207-12 pubmed
    ..In degenerative conditions as Parkinsonism, an excessive stimulation of mu binding sites might induce a pathological inhibition of calcium signals, thus contributing to modify the GP firing pattern and transmitter release. ..
  55. Dermitzaki E, Gravanis A, Venihaki M, Stournaras C, Margioris A. Opioids suppress basal and nicotine-induced catecholamine secretion via a stabilizing effect on actin filaments. Endocrinology. 2001;142:2022-31 pubmed
    ..It also appears that basal catecholamine secretion is associated with opioid-sensitive machinery regulating the continuous formation of short-lived areas of cortical actin filament disassembly...
  56. Gyires K, Ronai A. Supraspinal delta- and mu-opioid receptors mediate gastric mucosal protection in the rat. J Pharmacol Exp Ther. 2001;297:1010-5 pubmed
  57. Tubbs R, Porcaro W, Lee W, Blehar D, Carraway R, Przyklenk K, et al. Delta opiates increase ischemic tolerance in isolated rabbit jejunum. Acad Emerg Med. 2002;9:555-60 pubmed
    ..01). Treatment with the delta opioid agonist DADLE increases ischemic tolerance of isolated rabbit jejunum. ..
  58. Tang F, Borchardt R. Characterization of the efflux transporter(s) responsible for restricting intestinal mucosa permeation of an acyloxyalkoxy-based cyclic prodrug of the opioid peptide DADLE. Pharm Res. 2002;19:780-6 pubmed
  59. Maslov L, Sokolov A, Fedorova N, Lishmanov I, Karpov R. [Clinical response to agonists of mu and beta opiate receptors in patients with ischemic heart disease: effects of D-Ala2-Leu5-Arg6-enkephalin on hemodynamics, oxygen balance and lipid spectrum of blood]. Klin Med (Mosk). 2002;80:53-7 pubmed
    ..In addition, such treatment reduces oxygen consumption, levels of total cholesterol, triglycerides, low density lipoprotein cholesterol. ..
  60. May T. Squirreling away at Parkinson's. Drug Discov Today. 2003;8:51-2 pubmed
    ..A compound that triggers hibernation in ground squirrels can also protect brain cells from the lack of oxygen following a stroke. ..
  61. Hayashi T, SU T. Chronic [D-Ala2, D-Leu5]enkephalin treatment increases the nerve growth factor in adult mouse brain. Eur J Pharmacol. 2003;464:237-9 pubmed
    ..Glia-derived neurotrophic factor (GDNF) was not significantly affected. Thus, the neuroprotective action of DADLE may be mediated in part by NGF. ..
  62. Barg J, Belcheva M, Bem W, Lambourne B, McLachlan J, Tolman K, et al. Desipramine modulation of sigma and opioid peptide receptor expression in glial cells. Peptides. 1991;12:845-9 pubmed
    ..Opioid receptors in glial cell aggregates were primarily kappa, with few mu and delta sites. Desipramine increased Bmax values for kappa but not mu and delta. ..
  63. Liu J, Liao X, Gong Z, Qin B. The difference between methadone and morphine in regulation of delta-opioid receptors underlies the antagonistic effect of methadone on morphine-mediated cellular actions. Eur J Pharmacol. 1999;373:233-9 pubmed
    ..In addition, these results also indicate that the mechanisms of delta-opioid receptor desensitization induced by acute and chronic methadone treatment are different. ..
  64. Pivovarchik M. [State of the opioid system in rats with different sensitivity to ethanol]. Ukr Biokhim Zh (1999). 2001;73:138-40 pubmed
    ..Ethanol even at low dose produced changes in the midbrain opioid receptors which appeared after 6 hours. The response of the receptors and the content of opioids in plasma blood of rats with different DEIS were not identical. ..
  65. Das D, Lin S. Double-coated poly (butylcynanoacrylate) nanoparticulate delivery systems for brain targeting of dalargin via oral administration. J Pharm Sci. 2005;94:1343-53 pubmed
    ..However, further studies are required to elucidate the exact transport mechanism of PBCA-NDSs from gastrointestinal tract to brain...
  66. Drabek T, Han F, Garman R, Stezoski J, Tisherman S, Stezoski S, et al. Assessment of the delta opioid agonist DADLE in a rat model of lethal hemorrhage treated by emergency preservation and resuscitation. Resuscitation. 2008;77:220-8 pubmed publisher
    ..1+/-30.3 in D10 groups, respectively (p=0.3). OPC, NDS and HDS were not significantly different between groups. In conclusion, DADLE failed to confer benefit on functional or histological outcome in our model of prolonged rat EPR. ..
  67. Guo L, Qiu B, Jiang Y, You Z, Lin J, Chen G. Capillary electrophoresis chemiluminescent detection system equipped with a two-step postcolumn flow interface for detection of some enkephalin-related peptides labeled with acridinium ester. Electrophoresis. 2008;29:2348-55 pubmed publisher
    ..This CL detection system proved to be of high sensitivity, good repeatability, and relatively low cost. ..
  68. Chen Y, Siddalingappa B, Chan P, Benson H. Development of a chitosan-based nanoparticle formulation for delivery of a hydrophilic hexapeptide, dalargin. Biopolymers. 2008;90:663-70 pubmed publisher
    ..The use of either DS or SB-CD/DS mixture produced chitosan nanoparticles with small particle size, high dalargin entrapment efficiency, enhanced peptide stability, and sustained release characteristics. ..
  69. Xia Y, Haddad G. Major difference in the expression of delta- and mu-opioid receptors between turtle and rat brain. J Comp Neurol. 2001;436:202-10 pubmed
  70. Tsao L, Su T. Hibernation-induction peptide and cell death: [D-Ala2,D-Leu5]enkephalin blocks Bax-related apoptotic processes. Eur J Pharmacol. 2001;428:149-51 pubmed
    ..These results suggest that methamphetamine causes apoptosis by affecting the dynamics of Bax and that the neuroprotective property of DADLE may be due partly to its ability to potently block Bax-related apoptotic processes. ..
  71. Naryzhnaya N, Maslov L, Lishmanov Y, Gross G. Receptor specificity of the antiarrhythmic effect produced by opioid peptides Dalargin and DADLE during myocardial reperfusion. Bull Exp Biol Med. 2002;133:336-8 pubmed
    ..Blockade of mu-opioid receptors abolished the antiarrhythmic effect of these peptides. Hence, antiarrhythmic activity of dalargin and DADLE is primarily associated with activation of mu-opioid receptors. ..
  72. Schipke J, Nickel F, Gams E, Sunderdiek U. [Protective effects of a delta-opioid-receptor agonist and an oxygen radical scavenger on postischemic hearts]. Herz. 2004;29:331-40 pubmed
    ..Both substances improve the postischemic systolic and diastolic function and the relation between cardiac work and oxygen needed for this work. Thus, both substances offer promising properties in the clinic. ..
  73. Orlova E, Komarevtseva I. [Role of NO-synthase in stimulation of opiate receptors and kidney oxidative stress resistance]. Ukr Biokhim Zh (1999). 2004;76:97-102 pubmed
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