Hiromi Tsushima and Mayumi Mori
Department of Pharmacology, Nagoya City University Medical School, Kawasumi,
Mizuho-ku, Nagoya 467-8601, Japan
Abstract: Intracerebroventricular injections of capsaicin at
100 - 500 nmol elicited dose-dependent decreases in urine outflow volume
in anesthetized, hydrated rats. The capsaicin (500 nmol)-induced antidiuresis
was inhibited by pretreatment with CP96345 (30 nmol, a neurokinin-1-receptor
antagonist), but not by that with phenoxybenzamine (20 nmol, an alpha-adrenoceptor
antagonist), timolol (100 nmol, a beta-adrenoceptor antagonist) or atropine
(300 nmol, a muscarinic antagonist) into the hypothalamic supraoptic nucleus
(SON). Intravenous injections of d(CH2)5-D-Tyr(Et)VAVP
(50 microg/kg, a vasopressin-receptor antagonist) completely blocked the
antidiuresis. In intra-SON microdialysis experiments, acetylcholine concentration
in the perfusate of the capsaicin-injected rats was not different from that
of the vehicle-injected rats. These findings suggested that capsaicin stimulated
substance P release in the SON and caused the antidiuresis as a result of
the increased release of vasopressin into the circulation from the neurohypophysis
mediated through neurokinin-1 receptors in the SON.
Keywords: Supraoptic nucleus, Vasopressin, Substance P, Capsaicin, Neurokinin-1
receptor