Role of endogenous nociceptin in the regulation of arginine vasopressin release in conscious rats

The effects of central administration of the opioid-like peptide nociceptin (also known as orphanin FQ) were investigated on the secretion of arginine vasopressin (AVP) in response to dehydration and hyperosmolar or hypovolem ic stimulation in conscious rats. Intracerebroventricular (icv) administrat ion of nociceptin suppressed plasma AVP concentration in a dose-dependent m anner (0.1-10 mug/rat) in dehydrated rats, and the maximum effect was obtai ned 10 min after the administration (dehydration with 10 mug/rat nociceptin , 3.11 +/- 0.27 pg/ml vs. control, 10.32 +/- 0.96 pg/ml). The plasma AVP in crease in response to either hyperosmolality [ip injection of hypertonic sa line (HS) (600 mosml/kg)] or hypovolemia [ip injection of polyethylene glyc ol (PEG)] was also significantly blunted when nociceptin was injected icy ( HS with 10 mug/rat nociceptin, 1.16 +/- 0.09 pg/ml vs. control, 1.82 +/- 0. 30 pg/ml; PEG with 10 mug/rat nociceptin, 0.91 +/- 0.16 pg/ml vs. control, 2.41 +/- 0.26 pg/ml). Pretreatment with a selective opioid kappa -receptor antagonist, nor-binaltorphimine (1 mug/rat, icy) or naloxone (2.5 mg/rat, s c injection) did not reverse the inhibitory effects of nociceptin on AVP re lease. Moreover, when plasma AVP was suppressed by acute water loading, imm unoneutralization of endogenous nociceptin by antinociceptin-antiserum icy significantly reversed the suppression (0.57 +/- 0.12 pg/ml us. control, 0. 25 +/- 0.04 pg/ml). These results suggest that central nociceptin is physio logically involved in the control of AVP release through an inhibitory acti on.