Ulus I H, Millington W R, Buyukuysal R L, Kiran B K
Department of Pharmacology, University of Uludag Medical Faculty, Bursa, Turkey.
Biochem Pharmacol. 1988 Jul 15;37(14):2747-55. doi: 10.1016/0006-2952(88)90037-8.
These experiments examined the potency of choline as a cholinergic agonist at both muscarinic and nicotinic receptors in rat brain and peripheral tissues. Choline stimulated the contraction of isolated smooth muscle preparations of the stomach fundus, urinary bladder and trachea and reduced the frequency of spontaneous contractions of the right atrium at high micromolar and low millimolar concentrations. The potency of choline to elicit a biological response varied markedly among these tissues; EC50 values ranged between 0.41 mM in the fundus to 14.45 mM in the atrium. Choline also displaced [3H]quinuclidinyl benzilate binding in a concentration-dependent manner although, again, its potency varied among different brain regions (Ki = 1.2 to 3.5 mM) and peripheral tissues (Ki = 0.28 to 3.00 mM). Choline exhibited a comparable affinity for nicotinic receptors. It stimulated catecholamine release from the vascularly perfused adrenal gland (EC50 = 1.3 mM) and displaced L-[3H]nicotine binding to membrane preparations of brain and peripheral tissues (Ki = 0.38 to 1.17 mM). However, the concentration of choline required to bind to cholinergic receptors in most tissues was considerably higher than serum levels either in controls (8-13 microM) or following the administration of choline chloride (200 microM). These results clearly demonstrate that choline is a weak cholinergic agonist. Its potency is too low to account for the central nervous system effects produced by choline administration, although the direct activation of cholinergic receptors in several peripheral tissues may explain some of its side effects.
这些实验研究了胆碱作为胆碱能激动剂在大鼠脑和外周组织中的毒蕈碱受体和烟碱受体上的效力。胆碱在高微摩尔和低毫摩尔浓度下刺激胃底、膀胱和气管的离体平滑肌制剂收缩，并降低右心房的自发收缩频率。胆碱引发生物反应的效力在这些组织中差异显著；半数有效浓度（EC50）值在胃底为0.41 mM至心房为14.45 mM之间。胆碱还以浓度依赖性方式取代[3H]喹核醇基苯甲酸酯结合，不过其效力在不同脑区（解离常数Ki = 1.2至3.5 mM）和外周组织（Ki = 0.28至3.00 mM）中也有所不同。胆碱对烟碱受体表现出相当的亲和力。它刺激血管灌注的肾上腺释放儿茶酚胺（EC50 = 1.3 mM），并取代L-[3H]尼古丁与脑和外周组织膜制剂的结合（Ki = 0.38至1.17 mM）。然而，在大多数组织中，与胆碱能受体结合所需的胆碱浓度远高于对照组（8 - 13 microM）或给予氯化胆碱（200 microM）后的血清水平。这些结果清楚地表明胆碱是一种弱胆碱能激动剂。其效力过低，无法解释胆碱给药所产生的中枢神经系统效应，不过在几个外周组织中胆碱能受体的直接激活可能解释了它的一些副作用。
