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 supraoptic vasopressinergic nucleus (SON) in water-loaded and ethanol-anesthetized rats were examined. Substance P and its analog [D-Pro2, D-Trp7,9]SP induced marked decreases in urine outflow, with a ED50 value of approx. 0.4 and 0.9 nmol, respectively. The antidiuresis of SP was inhibited 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 with an intravenous injection of d(CH2)5-D-Tyr(Et)VAVP, an AVP (V1V2)-receptor antagonist. A prior injection of atropine, a muscarinic receptor 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.
Mori
M
M
Department of Pharmacology, Nagoya City University Medical School, Japan.
Tsushima
H
H
Matsuda
T
T
D000758:Anesthesia; D000818:Animals; D001127:Arginine Vasopressin / Q000502:physiology* / Q000652:urine; D001794:Blood Pressure / Q000187:drug effects; D004231:Diuresis / Q000187:drug effects*; D000431:Ethanol; D006339:Heart Rate / Q000187:drug effects; D007267:Injections; D008297:Male; D009994:Osmolar Concentration; D010286:Paraventricular Hypothalamic Nucleus / Q000502:physiology; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D012119:Respiration / Q000187:drug effects; D013373:Substance P / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013495:Supraoptic Nucleus / Q000502:physiology*; D014867:Water / Q000494:pharmacology*
D014867:Water; D001127:Arginine Vasopressin; D013373:Substance P; D000431:Ethanol; C032132:substance P, prolyl(2)-tryptophan(7,9)-