SUBSTANCE-P INJECTED INTO THE HYPOTHALAMIC SUPRAOPTIC NUCLEUS CAUSES ANTIDIURESIS THROUGH THE RELEASE OF ARGININE-VASOPRESSIN IN WATER-LOADED AND ETHANOL-ANESTHETIZED RATS

The effects of injection of substance P (SP) into the hypothalamic sup raoptic vasopressinergic nucleus (SON) in water-loaded and ethanol-ane sthetized rats were examined. Substance P and its analog [D-Pro2, D-Tr p7,9]SP induced marked decreases in urine outflow, with a ED50 value o f approx. 0.4 and 0.9 nmol, respectively. The antidiuresis of SP was i nhibited by a prior injection Of [D-Arg1, D-Trp7,9, Leu11]SP (spantide ), an SP-receptor antagonist into the SON. After the injection of SP, urine osmotic pressure was increased by threefold, and the urine level of arginine-vasopressin (AVP) was elevated by 70-fold. The effects of SP and [D-Pro2, D-Trp7,9]Sp were completely blocked by pretreatment w ith an intravenous injection of d(CH2)5-D-Tyr(Et)VAVP, an AVP (V1V2)-r eceptor antagonist. A prior injection of atropine, a muscarinic recept or antagonist, inhibited the effect of [D-Pro2 , D-Trp7,9]SP, but not that of SP. The results suggest that SP, injected into the SON, causes antidiuresis through the release of AVP. A possible mechanism for the antidiureses induced by SP and [D-Pro2, D-Trp7,9]SP is discussed.