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 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.
Tsushima
H
H
Department of Pharmacology, Nagoya City University Medical School, Nagoya, Japan.
Mori
M
M
D000109:Acetylcholine / Q000378:metabolism; D000758:Anesthesia; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001665:Binding Sites; D001713:Biphenyl Compounds / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology*; D004231:Diuresis / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D017551:Microdialysis; D010643:Phenoxybenzamine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018040:Receptors, Neurokinin-1 / Q000187:drug effects* / Q000502:physiology; D013373:Substance P / Q000378:metabolism*; D013495:Supraoptic Nucleus; D013997:Time Factors; D013999:Timolol / Q000494:pharmacology; D014667:Vasopressins / Q000378:metabolism*
D001713:Biphenyl Compounds; D006993:Hypnotics and Sedatives; D018040:Receptors, Neurokinin-1; D010643:Phenoxybenzamine; D014667:Vasopressins; D013373:Substance P; D001285:Atropine; D013999:Timolol; D000109:Acetylcholine; D002211:Capsaicin; C066892:CP 96345