[Phe1psi(CH2-NH)Gly2]nociceptin-(1 - 13)-NH2 activation of an inward rectifier as a partial agonist of ORL1 receptors in rat periaqueductal gray.
1. [Phe1psi(CH2-NH)Gly2]nociceptin-(1 - 13)-NH2 (Phepsi), a tridecapeptide analogue of orphanin FQ/nociceptin (OFQ/N), was introduced as a competitive antagonist of opioid receptor-like orphan receptor (ORL1) in guinea-pig ileum and mouse vas deferens preparations in vitro but was recently found to act as an agonist in vivo. 2. In the periaqueductal gray, a site enriched with both OFQ/N and ORL1 and involved in OFQ/N-induced hyperalgesia and anti-analgesia, the effects of Phepsi and OFQ/N on the membrane current were studied using whole cell patch clamp recording technique in rat brain slices. 3. OFQ/N (0.01 - 1 microM) activated an inwardly rectifying type of K+ channels in ventrolateral neurons of PAG. Phepsi (0.03 - 1 microM), like OFQ/N, also activated this inward rectifier but had only 30% efficacy of OFQ/N. 4 At maximal effective concentration (1 microM), Phepsi reversed the increment of K+ conductance induced by OFQ/N (300 nM) by 46%. On the other hand, Phepsi also prevented the effect of OFQ/N if pretreated before OFQ/N. 5 It is suggested that Phepsi acts as a partial agonist of ORL1 that mediates the activation of inwardly rectifying K+ channels in ventrolateral neurons of rat periaqueductal gray.
Chiou
L C
LC
Department of Pharmacology, College of Medicine, National Taiwan University, No 1, Jen-Ai Road, Section 1, Taipei 100, Taipei, Taiwan. lcchiou@ha.mc.ntu.edu.tw
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009292:Narcotic Antagonists; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018847:Opioid Peptides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000494:pharmacology*; D010487:Periaqueductal Gray / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000819:agonists* / Q000502:physiology; D013997:Time Factors; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D009292:Narcotic Antagonists; D018847:Opioid Peptides; D010446:Peptide Fragments; D011188:Potassium; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C114149:nociceptin (1-13)-NH2, Phe(1)-psi(CH2-NH)-Gly(2)-; C000722285:Oprl1 protein, rat