Arita M, Wada A, Takara H, Izumi F
Department of Pharmacology, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
J Pharmacol Exp Ther. 1987 Oct;243(1):342-8.
In bovine adrenal medullary cells we investigated the effects of antidepressants on ionic channels and secretion of catecholamines. Tricyclic (imipramine, amitriptyline and nortriptyline) and tetracyclic (maprotiline and mianserin) antidepressants inhibited carbachol-induced influx of 22Na, 45Ca and secretion of catecholamines (IC50, 14-96 microM). Influx of 22Na, 45Ca and secretion of catecholamines due to veratridine also were inhibited by these drugs (IC50, 10-17 microM). However, antidepressants did not suppress high concentration of K-induced 45Ca influx and catecholamine secretion, suggesting that antidepressants do not inhibit voltage-dependent Ca channels. [3H]Imipramine bound specifically to adrenal medullary cells. Binding was saturable, reversible and with two different equilibrium dissociation constants (13.3 and 165.0 microM). Tricyclic and tetracyclic antidepressants competed for the specific binding of [3H]imipramine at the same concentrations as they inhibited 22Na influx caused by carbachol or veratridine. Carbachol, d-tubocurarine, hexamethonium, tetrodotoxin, veratridine and scorpion venom did not inhibit the specific binding of [3H]imipramine. These results suggest that tricyclic and tetracyclic antidepressants bind to two populations of binding sites which are functionally associated with nicotinic receptor-associated ionic channels and with voltage-dependent Na channels, and inhibit Na influx. Inhibition of Na influx leads to the reduction of Ca influx and catecholamine secretion caused by carbachol or veratridine.
在牛肾上腺髓质细胞中，我们研究了抗抑郁药对离子通道和儿茶酚胺分泌的影响。三环类（丙咪嗪、阿米替林和去甲替林）和四环类（马普替林和米安色林）抗抑郁药抑制了卡巴胆碱诱导的22Na、45Ca内流以及儿茶酚胺的分泌（半数抑制浓度，14 - 96微摩尔）。这些药物也抑制了由藜芦碱引起的22Na、45Ca内流以及儿茶酚胺的分泌（半数抑制浓度，10 - 17微摩尔）。然而，抗抑郁药并未抑制高浓度钾诱导的45Ca内流和儿茶酚胺分泌，这表明抗抑郁药并不抑制电压依赖性钙通道。[3H]丙咪嗪特异性结合于肾上腺髓质细胞。结合具有饱和性、可逆性，且有两个不同的平衡解离常数（13.3和165.0微摩尔）。三环类和四环类抗抑郁药在抑制卡巴胆碱或藜芦碱引起的22Na内流的相同浓度下，竞争[3H]丙咪嗪的特异性结合。卡巴胆碱、d - 筒箭毒碱、六甲铵、河豚毒素、藜芦碱和蝎毒均不抑制[3H]丙咪嗪的特异性结合。这些结果表明，三环类和四环类抗抑郁药结合于两类与烟碱受体相关离子通道以及电压依赖性钠通道功能相关的结合位点，并抑制钠内流。钠内流的抑制导致由卡巴胆碱或藜芦碱引起的钙内流和儿茶酚胺分泌减少。
