Central injections of capsaicin cause antidiuresis mediated through neurokinin-1 receptors in rat hypothalamus and vasopressin release

Intracerebroventricular injections of capsaicin at 100-500 nmol elicited do se-dependent decreases in urine outflow volume in anesthetized, hydrated ra ts. The capsaicin (500 nmol)-induced antidiuresis was inhibited by pretreat ment with CP96345 (30 nmol, a neurokinin-l -receptor antagonist), but not b y that with phenoxybenzamine (20 nmol, an alpha-adrenoceptor antagonist), t imolol (100 nmol, a beta-adrenoceptor antagonist) or atropine (300 nmol, a muscarinic antagonist) into the hypothalamic supraoptic nucleus (SON). Intr avenous injections of d(CH2)(5)-D-Tyr(Et)VAVP (50 mu g/kg, a vasopressin-re ceptor antagonist) completely blocked the antidiuresis. In intra-SON microd ialysis experiments, acetylcholine concentration in the perfusate of the ca psaicin-injected rats was not different from that of the vehicle-injected r ats. These findings suggested that capsaicin stimulated substance P release in the SON and caused the antidiuresis as a result of the increased releas e of vasopressin into the circulation from the neurohypophysis mediated thr ough neurokinin-l receptors in the SON.