Prejunctional modulation of sensory-motor nerve-mediated vasodilatation of the rat mesenteric arterial bed by opioid peptides.
In the rat isolated mesenteric arterial bed, perivascular nerve stimulation in the presence of guanethidine (5 microM) and methoxamine (30-50 microM), elicited frequency-dependent vasodilatation due to activation of sensory-motor nerves. The present study examined the modulation of this sensory-motor activity by opioid peptides. The mu-selective opioid agonist [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO) inhibited vasodilator responses to sensory-motor nerve stimulation. The native enkephalins [Met5]enkephalin (mENK) and [Leu5]enkephalin (IENK) were less potent, whereas the delta-selective agonist DPDPE was without effect. Naloxone (30 nM) reversed the inhibitory effects of both DAMGO and mENK. The delta opioid antagonist ICI 174864 (0.1 microM) had no effect on the inhibition by mENK. Inhibitory effects of the kappa opioid-selective agonist 3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]-methanesulfonate hydrate (U-50,488H) on sensory-motor nerve-induced vasodilatation were unaffected by naloxone (0.3 microM) or by the kappa opioid receptor-selective antagonist (-)-5,9 alpha-diethyl-2-(3-furylmethyl)-2'-hydroxy-6,7-benzomorphane (MR 2266). Neither DAMGO nor mENK inhibited vasodilator responses to calcitonin gene-related peptide (CGRP), the principle vasodilator transmitter released from sensory-motor nerves in the rat mesenteric arterial bed or to the sensory neurotoxin capsaicin. In mesenteric beds from reserpine-treated rats (to abolish the catecholamine, but not opioid, content of sympathetic nerves) naloxone facilitated sensory-motor nerve-mediated vasodilatation. These results suggest that sensory-motor neurotransmission in the rat mesenteric arterial bed is inhibited by prejunctional mu, but not by delta or kappa opioid receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Ralevic
V
V
Department of Anatomy and Developmental Biology, University College London, United Kingdom.
Rubino
A
A
Burnstock
G
G
D000818:Animals; D004558:Electric Stimulation; D004723:Endorphins / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D009270:Naloxone / Q000494:pharmacology; D009475:Neurons, Afferent / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000502:physiology; D013564:Sympathetic Nervous System / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
D004723:Endorphins; D011957:Receptors, Opioid; D009270:Naloxone