Lc. Chiou, [Phe(1)psi(CH2-NH)Gly(2)]nociceptin-(1-13)-NH2 activation of an inward rectifier as a partial agonist of ORL1 receptors in rat periaqueductal gray, BR J PHARM, 128(1), 1999, pp. 103-107
1 [Phe(1)psi(CH2-NH)Gly(2)]nociceptin-(1-13)-NH2 (Phe psi), a tridecapeptid
e analogue of orphanin FQ/nociceptin (OFQ/N), was introduced as a competiti
ve antagonist of opioid receptor-like orphan receptor (ORL1) in guinea-pig
ileum and mouse vas deferens preparations in vitro but was recently found t
o 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 P
he psi and OFQ/N on the membrane current were studied using whole cell patc
h clamp recording technique in rat brain slices.
3 OFQ/N (0.01-1 mu M) activated an inwardly rectifying type of K+ channels
in ventrolateral neurons of PAG. Phe psi (0.03 - 1 mu M), like OFQ/N, also
activated this inward rectifier but had only 30% efficacy of OFQ/N.
4 At maximal effective concentration (1 mu M), Phe psi reversed the increme
nt of K+ conductance induced by OFQ/N (300 nM) by 46%. On the other hand, P
he psi also prevented the effect of OFQ/N if pretreated before OFQ/N.
5 It is suggested that Phe psi acts as a partial agonist of ORL1 that media
tes the activation of inwardly rectifying K+ channels in ventrolateral neur
ons of rat periaqueductal gray.