Mori M, Tsushima H, Matsuda T
Department of Pharmacology, Nagoya City University Medical School, Japan.
Jpn J Pharmacol. 1993 May;62(1):49-56. doi: 10.1254/jjp.62.49.
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.
研究了向水负荷和乙醇麻醉大鼠的下丘脑视上核加压素能核（SON）注射P物质（SP）的作用。P物质及其类似物[D-脯氨酸2，D-色氨酸7,9]SP可使尿流量显著减少，其半数有效剂量（ED50）值分别约为0.4和0.9 nmol。预先向SON注射SP受体拮抗剂[D-精氨酸1，D-色氨酸7,9，亮氨酸11]SP（spantide）可抑制SP的抗利尿作用。注射SP后，尿渗透压增加了两倍，精氨酸加压素（AVP）的尿水平升高了70倍。静脉注射AVP（V1V2）受体拮抗剂d(CH2)5-D-Tyr(Et)VAVP预处理可完全阻断SP和[D-脯氨酸2，D-色氨酸7,9]SP的作用。预先注射毒蕈碱受体拮抗剂阿托品可抑制[D-脯氨酸2，D-色氨酸7,9]SP的作用，但不抑制SP的作用。结果表明，注射到SON中的SP通过释放AVP引起抗利尿作用。本文讨论了SP和[D-脯氨酸2，D-色氨酸7,9]SP诱导抗利尿作用的可能机制。
