Schneider B, Ganten D, Lang R E, Unger T
Eur J Pharmacol. 1986 Nov 12;131(1):31-7. doi: 10.1016/0014-2999(86)90512-1.
The influence of GABA-ergic stimulation on the centrally evoked pressor and tachycardic responses to substance P (SP) was investigated in conscious rats. Intracerebroventricular (i.c.v.) pretreatment with the potent GABA agonist muscimol attenuated the pressor responses to i.c.v. administered SP in a dose-dependent and reversible fashion. Inhibition was maximal 5-60 min after muscimol injection and lasted up to 3 h. In contrast, the increases in heart rate in response to i.c.v. administered SP were not consistently inhibited by muscimol. Central pretreatment with muscimol prevented the increase of plasma adrenaline but not of plasma noradrenaline in response to i.c.v. administered SP. Our results demonstrate that the GABA-ergic system can exert an inhibitory control on pathways mediating the central pressor actions of SP. The selective inhibition of adrenaline secretion by muscimol implies that suppression of sympathetic outflow to the adrenal gland may be involved as an important mechanism. In addition, our findings point to a dissociation between pathways mediating the pressor and tachycardic effects of SP.
在清醒大鼠中研究了γ-氨基丁酸（GABA）能刺激对中枢诱发的对P物质（SP）的升压和心动过速反应的影响。用强效GABA激动剂蝇蕈醇进行脑室内（i.c.v.）预处理，以剂量依赖和可逆的方式减弱了对i.c.v.给予的SP的升压反应。抑制作用在蝇蕈醇注射后5 - 60分钟达到最大，并持续长达3小时。相比之下，蝇蕈醇并未始终抑制对i.c.v.给予的SP的心率增加。用蝇蕈醇进行中枢预处理可防止对i.c.v.给予的SP时血浆肾上腺素的增加，但不能防止血浆去甲肾上腺素的增加。我们的结果表明，GABA能系统可对介导SP中枢升压作用的通路发挥抑制性控制。蝇蕈醇对肾上腺素分泌的选择性抑制意味着抑制肾上腺的交感神经流出可能是一个重要机制。此外，我们的研究结果表明，介导SP升压和心动过速作用的通路之间存在分离。
