Physiology and pathophysiology of drug receptor mechanisms

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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.