Inhibitory action of leumorphin on vasopressin secretion in conscious rats

To elucidate the role of leumorphin, a kappa-agonist derived from proenkephalin-B (neoendorphin/dynorphin precursor), in the control of arginine vasopressin (AVP) secretion, we examined the effects of intracerebroventricular (icv) administration of leumorphin on AVP secretion under basal and stimulated conditions in conscious unrestrained rats. Intracerebroventricular injection of leumorphin (60 or 600 pmol) significantly inhibited basal AVP secretion. In 72-h water-deprived rats, icv injection of leumorphin (60 or 600 pmol) also suppressed AVP secretion in a dose-dependent manner. The AVP response induced by icv injection of angiotensin II (100 pmol) was significantly decreased by the simultaneous icv injection of leumorphin (6-600 pmol) in a dose-dependent manner. Intracerebroventricular administration of leumorphin (600 pmol) also reduced the AVP secretion stimulated by icv injection of carbachol (50 pmol). Intravenous pretreatment with naloxone (0.5 mg/kg BW) diminished the inhibitory action of leumorphin (60 pmol) on AVP secretion. However, no effect on AVP secretion was observed after iv injection of leumorphin (600 pmol). These results indicate that leumorphin possesses a potent inhibitory effect on AVP secretion, suggesting its important role in the regulation of AVP secretion in the brain.