Szmigielska H, Szmigielski A, Szadowska A
Department of Pharmacodynamics, Medical Academy, Lódź, Poland.
Pol J Pharmacol Pharm. 1989 Nov-Dec;41(6):629-37.
Administration of diazepam, an agonist of benzodiazepine receptors, and muscimol, an agonist of GABA(A) receptors, resulted in an increase in cytosol GABA-modulin in hypothalamus and cerebellum. Low dose of muscimol, ineffective by itself, completely antagonized the isoniazid, bicuculline and picrotoxin-induced decrease in GABA-modulin activity. In contrast, low dose of diazepam was able to block only the action of isoniazid. That confirms different mechanism of action of muscimol and diazepam. The increase in cytosol GABA-modulin activity in the anterior and posterior hypothalamus of spontaneously hypertensive rats (SHR) and of vasopressin hypertensive rats required much higher doses of muscimol than in normotensive animals showing subsensitivity of GABA(A) receptors in these brain structures. In contrast, the sensitivities of GABA(A) receptors in the cerebellum and of benzodiazepine receptors in the hypothalamus and cerebellum were equal to hypertensive and normotensive rats.
给予苯二氮䓬受体激动剂地西泮以及γ-氨基丁酸A（GABA(A)）受体激动剂蝇蕈醇后，下丘脑和小脑中的胞质GABA调节蛋白增加。低剂量的蝇蕈醇本身无效，但能完全拮抗异烟肼、荷包牡丹碱和印防己毒素诱导的GABA调节蛋白活性降低。相比之下，低剂量的地西泮仅能阻断异烟肼的作用。这证实了蝇蕈醇和地西泮的作用机制不同。自发性高血压大鼠（SHR）和血管加压素性高血压大鼠的下丘脑前后部胞质GABA调节蛋白活性增加所需的蝇蕈醇剂量比正常血压动物高得多，表明这些脑结构中的GABA(A)受体存在亚敏感性。相比之下，小脑内GABA(A)受体以及下丘脑和小脑中苯二氮䓬受体的敏感性在高血压大鼠和正常血压大鼠中是相同的。
