Effect of opioid receptor antagonists on vasodilator nerve actions in the perfused rat mesentery.
Our previous work suggests that opioid peptides modulate sensory nerves in the perfused rat mesentery. Therefore we tested the hypothesis that opioids are involved in the ongoing regulation of sensory nerve activity using selective opioid receptor antagonists. In the presence of guanethidine and methoxamine, transmural nerve stimulation caused a vasodilator response which was potentiated significantly by naloxone (3 x 10(-7) M). However, naloxone did not affect vasodilator responses to exogenous calcitonin gene related peptide. IC1 174.864 (3 x 10(-7) M), a selective delta receptor antagonist, had no effect on vasodilator responses to transmural nerve stimulation. In contrast CTOP (D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Phe-Thr-NH2) (3 x 10(-7) M), a selective mu receptor antagonist, significantly inhibited vasodilator responses to transmural nerve stimulation, effects which were abolished by naloxone treatment. In preparations pretreated with beta-FNA (beta-funaltrexamine HCl), an irreversible mu receptor antagonist, naloxone no longer potentiated vasodilator responses to transmural nerve stimulation. These results suggest that potentiation of vasodilator responses to transmural nerve stimulation by naloxone may be due to blockade of mu receptors, resulting in a reduced inhibitory modulation by endogenous opioids. These findings support the contention that prejunctional opioid receptors on sensory nerves may play a role in modulating activity of the cardiovascular system.
Department of Pharmacology, College of Medicine University of California, Irvine 92717.
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D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D004558:Electric Stimulation; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D004745:Enkephalins / Q000494:pharmacology; D006145:Guanethidine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000294:innervation* / Q000502:physiology; D008729:Methoxamine / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000294:innervation* / Q000502:physiology; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D004745:Enkephalins; D009292:Narcotic Antagonists; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C049352:phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide; D009270:Naloxone; D013004:Somatostatin; D004743:Enkephalin, Leucine; D009271:Naltrexone; C024524:beta-funaltrexamine; C040643:N,N-diallyl-tyrosyl-alpha-aminoisobutyric acid-phenylalanyl-leucine; D008729:Methoxamine; D015740:Calcitonin Gene-Related Peptide; D006145:Guanethidine