Szmigielski A, Szadowska A, Szmigielska H, Zalewska J
Pol J Pharmacol Pharm. 1985 Nov-Dec;37(6):773-81.
Administration of clonidine produced biphasic changes in the type II inhibitor activity (endogenous inhibitor of protein kinases which specifically regulates phosphorylation mediated by cGMP-dependent system). Small doses of clonidine (10-50 micrograms/kg) produced an increase while large doses (200-1000 micrograms/kg) induced a decrease in the type II inhibitor activity. The both actions of clonidine were greatly reduced in vasopressin hypertensive rats suggesting subsensitivity of alpha 2-adrenergic receptors. Subsensitivity of postsynaptic alpha 2-receptors was also observed in anterior hypothalamus in in vitro experiments. Incubation of anterior and posterior hypothalamic slices with clonidine resulted in concentration-dependent increase in cGMP content and a decrease in the type II inhibitor activity. The clonidine action in anterior hypothalamus of vasopressin-hypertensive rats was greatly reduced. In contrast, the clonidine action in posterior hypothalamus was the same in vasopressin-hypertensive as in the control rats.
可乐定的给药引起II型抑制剂活性（蛋白激酶的内源性抑制剂，特异性调节由cGMP依赖性系统介导的磷酸化）出现双相变化。小剂量可乐定（10 - 50微克/千克）可使其活性增加，而大剂量（200 - 1000微克/千克）则导致II型抑制剂活性降低。在血管升压素性高血压大鼠中，可乐定的这两种作用均显著减弱，提示α2 - 肾上腺素能受体存在亚敏感性。在体外实验中，前下丘脑也观察到了突触后α2受体的亚敏感性。用可乐定孵育下丘脑前、后叶切片，可导致cGMP含量呈浓度依赖性增加以及II型抑制剂活性降低。可乐定对血管升压素性高血压大鼠前下丘脑的作用显著减弱。相反，可乐定对后下丘脑的作用在血管升压素性高血压大鼠与对照大鼠中相同。
