Physiology and pathophysiology of drug receptor mechanisms

本课题组研究了药物受体在各器官中的生理和病理生理作用，得到以下结果和结论：1)原代培养神经元持续暴露于毒蕈碱激动剂和/或拮抗剂诱导受体下调和/或上调，这些变化伴随着与受体偶联的第二信使系统的变化。2)各种药物对心肌缺血引起的心肌病的保护作用离不开膜稳定作用。3)血管内皮细胞的增殖与儿茶酚胺对α _1-肾上腺素受体的刺激有关，在动脉硬化的进展中起重要作用。4)同时使用肾上腺素能阻滞剂、k-阿片受体激动剂和钙通道阻滞剂可阻止吗啡功能耐受的发展。5)钾通道打开剂选择性抑制IP_3诱导的CA^<++>在心脏的释放。6)多巴胺过量释放时，中枢多巴胺D_1受体被激活。7)血管平滑肌肾上腺素能受体的功能随年龄的增长而下降，而胆碱能受体的功能不受年龄的影响。8)冠状动脉中β受体以β _1型为主。9) NO激活鸟苷酸环化酶导致cGMP升高，介导脑动脉扩张。10)内皮素通过刺激神经节内血栓素A_2的产生和激活Ca^<++>依赖的K^+通道来抑制神经节间传导。11)下丘脑同时具有P下受体和阿片受体，它们参与尿流出的调节。

Physiological and pathophysiological roles of drug receptors in various organs were investigated in this research group and the following results and conclusions were obtained. 1) Continuous exposure of primary cultured neurons to muscarinic agonists and/or antagonists induced down- and/or up-regulation of the receptor and these changes were accompanied with those in second messenger systems coupled with the receptor. 2) The membrane stabilizing effect was essential for the protecting effect of various drugs on cardiac myopathy induced by cardiac ischemia. 3) The proliferation of vascular endotherial cells, which plays an important role in the progession of arteriosclerosis, was associated with the stimulation of alpha_1-adrenoceptor by cathecholamines. 4) The development of functional tolerance to morphine was prevented by the concomitant administrations of adrenergic blockers, k-opioid receptor agonist and calcium channel blockers. 5) Potassium channel opener selectively inhibited IP_3 -induced CA^<++> release in the heart. 6) Central dopamine D_1 receptor was operated when the excess of dopamine release was induced. 7) The function of adrenergic receptors in vascular smooth muscle showed a decrease with the progression of aging, while cholinergic receptors in this tissue were not affected significantly by aging. 8) The bata-receptors in the coronary artery were mostly beta_1 type. 9) The dilatation of cerebral arteries was mediated by the increase of cGMP caused by the activation of guanylate cyclase with NO. 10) Endothelin inhibited ganglionic transmission by ganglionic stimulation of thromboxane A_2 production as well as postganglionic activation of Ca^<++> dependent K^+channel. 11) The hypothalamus possessed both subsaince P and opioid receptors which are involved in the regulation of urinary outflow.