Trifluoperazine Inhibits 45Ca2+ Uptake and Catecholamine Secretion and Synthesis in Adrenal Medullary Cells |
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Authors: | Akihiko Wada Nobuyuki Yanagihara Futoshi Izumi Seishi Sakurai Hideyuki Kobayashi |
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Affiliation: | Department of Pharmacology, University of Occupational and Environmental Health, School of Medicine, Fukuoka, Japan |
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Abstract: | Abstract: In isolated adrenal medullary cells, carbamyl-choline and high K+ cause the calcium-dependent secretion of catecholamines with a simultaneous increase in the synthesis of 14C-catecholamines from [14C]tyrosine. In these cells, trifluoperazine, a selective antagonist of calmodulin, inhibited both the secretion and synthesis of catecholamines. The stimulatory effect of carbamyl-choline was inhibited to a greater extent than that of high K+. The inhibitory effect of trifluoperazine on carbamylcholine-evoked secretion of catecholamines was not overcome by an increase in either carbamylcholine or calcium concentration, showing that inhibition by trifluoperazine occurs by a mechanism distinct from competitive antagonism at the cholinergic receptor and from direct inactivation of calcium channels. Doses of trifluoperazine that inhibited catecholamine secretion and synthesis also inhibited the uptake of radioactive calcium by the cells. These results suggest that trifluoperazine inhibits the secretion and synthesis of catecholamines mainly due to its inhibition of calcium uptake. Trifluoperazine seems to inhibit calcium uptake by uncoupling the linkage between cholinergic receptor stimulation and calcium channel activation. |
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Keywords: | Adrenal medulla Catecholamine secretion and synthesis 45Ca2+ uptake Trifluoperazine Calmodulin |
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