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, [Tyr1]-nociceptin, noci ceptin-(2-17), nociceptin-(1-11), and nociceptin-(1-7) were compared in the systemic vascu lar 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 noci ceptin and [Tyr1]-nociceptin arc mediated by the activation of a naloxone-insensitive opioid receptor and arc not dependent on the presence of Phc at the N-terminus of the nociceptin sequence. Moreover, the present results show that nociceptin-(2-17). nociceptin-(1-11), and nociccptin-(1-7) do not after SAP in the rabbit, indicating that peptide chain length is important for the expression of vasodepressor activity.
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