Analysis of Vasodepressor Responses to Nociceptin and Nociceptin Analogs in the Systemic Vascular Bed of the Anesthetized Rabbit In Vivo.
Background: The heptadecapeptide nociceptin, also known as Orphanin FQ, is a recently discovered endogenous ligand for the opioid-like G-protein-coupled receptor ORL(1). Methods and Results: In the present study, responses to nociceptin, [Tyr(1)]-nociceptin, nociceptin-(2-17), nociceptin-(1-11), and nociceptin-(1-7) were compared in the systemic vascular bed of the rabbit. Nociceptin and [Tyr(1)]-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, [Tyr(1)]-nociceptin and nocicpetin were similar in potency. However, nocicpetin-(2-17), nocicpetin-(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 [Tyr(1)]-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 [Tyr(1)]-nocicpetin are mediated by the activation of a naloxene-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.
Champion
HC
Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana, USA
Bivalacqua
TJ
Rauchwarger
A
McWilliams
SM
McNamara
DB
Kadowitz
PJ