Functional Selectivity of Nociceptin/Orphanin FQ Peptide Receptor Partial Agonists on Cardiovascular and Renal Function

摘要: The opioid-like peptide nociceptin/orphanin FQ (N/OFQ) produces marked cardiovascular and renal responses after central or peripheral administration in rats. Due to their ability behave as full/partial agonists antagonists different cellular tissue assays, the present studies were performed determine how compounds classified N/OFQ (NOP) receptor partial ([F/G]N/OFQ(1-13)-NH 2 , Ac-RYYRIK-NH Ac-RYYRWK-NH ) affect function vivo. In conscious Sprague-Dawley rats, intracerebroventricular (i.c.v.) of each three NOP ligands produced profound (depressor), excretory (water diuresis), sympathetic nerve activity (inhibitory) that similar those by i.c.v. injection native ligand N/OFQ. contrast, other groups intravenous (i.v.) bolus these same unlike N/OFQ; evoked an immediate bradycardia hypotension with no change urine output, whereas all purported elicited a subtle slow onset hypotension, heart rate, water diuresis. studies, i.v. pretreatment rats prevented/attenuated depressor effects subsequent challenge without affecting Together, findings demonstrate produce functionally selective on ranging from full agonist (i.c.v., depressor; i.v., (i.v., submaximal hypotension) antagonist blockade N/OFQ-evoked behavior.