title: Vasorelaxant responses to endomorphin1[psi] and endomorphin2[psi], analogues of endomorphins, in rat aorta rings.
abstract: Endomorphin-1 (Tyr-Pro-Trp-Phe-NH2, EM1) and endomorphin-2 (Tyr-Pro-Phe-Phe-NH2, EM2), the endogenous selective mu-opioid receptor agonists, can inhibit phenylephrine (PE) induced contraction which is related to the release of nitric oxide from vascular endothelium in aorta rings of rats and rabbits. The reduced (CH2NH) amide bond is a useful peptide bond surrogate in the design of opioid mimetics because it could enhance conformational flexibility and metabolic stability. The present work was designed to investigate the vascular activities of interrelated endomorphin analogues: endomorphin-1[psi] (Tyr[psi(CH2NH)]Pro-Trp-Phe-NH2, EM1[psi]) and endomorphin-2[psi] (Tyr[psi(CH2NH)]Pro-Phe-Phe-NH2, EM2[psi]). The effect of EM1[psi] (1, 2, 3, 4, 5 microM) and EM2[psi] (0.001, 0.01, 0.1, 1, 5 microM) were evaluated on rat thoracic aortic rings pre-contracted with PE (0.1 microM). EM1[psi] and EM2[psi] both caused a concentration-dependent relaxation. The IC50 of EM1[psi] and EM2[psi] was 3.332 microM and 1.226 microM, respectively. The vasorelaxant effect of EMs[psi] is 216.9 and 237.1 fold more potent than EMs. Moreover, the vasorelaxant effect of EMs[psi] was blocked by naloxone (NaCl, 1 microM) and was reduced by N(omega)-nitro-L-arginine (L-NNA, 1 microM) and removal of endothelium. The present study demonstrated that EMs[psi] had more potent vasorelaxant effects and their activities were naloxone-sensitive and endothelium-dependent and partially NO-dependent, similar to the mechanism of parent EMs.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Life Science, Lanzhou University, Lanzhou, P.R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Feng
authors.forename: Qian-Yu
authors.initials: QY
authors.lastname: Zhao
authors.forename: Qiang
authors.initials: Q
authors.lastname: Chen
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors; D009842:Oligopeptides / Q000494:pharmacology*; D010656:Phenylephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014665:Vasodilator Agents
chemical_list: D004791:Enzyme Inhibitors; D009292:Narcotic Antagonists; D009842:Oligopeptides; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C105293:endomorphin 1; D010656:Phenylephrine; D009270:Naloxone; C105294:endomorphin 2; D052250:Nitric Oxide Synthase Type III; D019331:NG-Nitroarginine Methyl Ester