Analysis of vasodepressor responses to nociceptin and nociceptin analogs in the systemic vascular bed of the anesthetized rabbit in vivo

H. C. Champion, T. J. Bivalacqua, A. Rauchwarger, S. M. McWilliams, D. B. McNamara, P. J. Kadowitz

Research output: Contribution to journalArticlepeer-review

Abstract

Background: The heptadecapeptide nociceptin, also known as Orphanin FQ, is a recently discovered endogenous ligand for the opioid-like G-protein- coupled receptor ORL1. Methods and Results: In the present study, responses to nociceptin, [Tyr1]-nociceptin, nociceptin-(2-17), nociceptin-(1-11), and nociceptin-(1-7) were compared in the systemic vascular bed of the rabbit. Nociceptin and [Tyr1]-nociceptin induced dose related decreases in systemic arterial pressure (SAP) when injected in doses of 1-30 nmol/kg intravenous (IV); in terms of relative vasodepressor activity, [Tyr1]-nociceptin and nociceptin were similar in potency. However, nociceptin-(2-17), nociceptin- (1-11), and nociceptin-(1-7) had no effect on SAP when injected in doses up to 30 nmol/kg IV. The decreases in SAP in response to nociceptin and [Tyr1]- nociceptin were not altered by the opioid receptor antagonist naloxone at a time when depressor responses to methionine-enkephalin were reduced significantly. Conclusions: The results of the present study show that vasodepressor responses to nociceptin and [Tyr1]-nociceptin are mediated by the activation of a naloxone-insensitive opioid receptor and are not dependent on the presence of Phe at the N-terminus of the nociceptin sequence. Moreover, the present results show that nociceptin-(2-17), nociceptin-(1-11), and nociceptin-(1-7) do not alter SAP in the rabbit, indicating that peptide chain length is important for the expression of vasodepressor activity.

Original languageEnglish (US)
Pages (from-to)247-252
Number of pages6
JournalJournal of Cardiovascular Pharmacology and Therapeutics
Volume3
Issue number3
DOIs
StatePublished - Jan 1 1998
Externally publishedYes

Keywords

  • Opioid receptors
  • Orphanin FQ
  • Vasodepressor activity

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine
  • Pharmacology (medical)

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