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 hypovolemic stimulation in conscious rats. Intracerebroventricular (icv) administration of nociceptin suppressed plasma AVP concentration in a dose-dependent manner (0.1–10 μg/rat) in dehydrated rats, and the maximum effect was obtained 10 min after the administration (dehydration with 10 μg/rat nociceptin, 3.11± 0.27 pg/ml vs. control, 10.32 ± 0.96 pg/ml). The plasma AVP increase in response to either hyperosmolality [ip injection of hypertonic saline (HS) (600 mosml/kg)] or hypovolemia[ ip injection of polyethylene glycol (PEG)] was also significantly blunted when nociceptin was injected icv (HS with 10 μg/rat nociceptin, 1.16 ± 0.09 pg/ml vs. control, 1.82 ± 0.30 pg/ml; PEG with 10 μg/rat nociceptin, 0.91 ± 0.16 pg/ml vs. control, 2.41 ± 0.26 pg/ml). Pretreatment with a selective opioid κ-receptor antagonist, nor-binaltorphimine (1 μg/rat, icv) or naloxone (2.5 mg/rat, sc injection) did not reverse the inhibitory effects of nociceptin on AVP release. Moreover, when plasma AVP was suppressed by acute water loading, immunoneutralization of endogenous nociceptin by antinociceptin-antiserum icv significantly reversed the suppression (0.57 ± 0.12 pg/ml vs. control, 0.25 ± 0.04 pg/ml). These results suggest that central nociceptin is physiologically involved in the control of AVP release through an inhibitory action.