Premium
Differential inhibition of catecholamine secretion by amitriptyline through blockage of nicotinic receptors, sodium channels, and calcium channels in bovine adrenal chromaffin cells
Author(s) -
Park TaeJu,
Shin SoYoung,
Suh ByungChang,
Suh EunKyung,
Lee IhnSoon,
Kim YongSik,
Kim KyongTai
Publication year - 1998
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/(sici)1098-2396(199807)29:3<248::aid-syn7>3.0.co;2-6
Subject(s) - catecholamine , chemistry , nicotinic agonist , chromaffin cell , secretion , endocrinology , receptor , calcium , pharmacology , medicine , adrenal medulla , biology , biochemistry , organic chemistry
Abstract We investigated the effects of amitriptyline, a tricyclic antidepressant, on [ 3 H]norepinephrine ([ 3 H]NE) secretion and ion flux in bovine adrenal chromaffin cells. Amitriptyline inhibited [ 3 H]NE secretion induced by 1,1‐dimethyl‐4‐phenylpiperazinium iodide (DMPP) and 70 mM K + . The half maximal inhibitory concentration (IC 50 ) was 2 μM and 9 μM, respectively. Amitriptyline also inhibited the elevation of cytosolic calcium ([Ca 2+ ] i ) induced by DMPP and 70 mM K + with IC 50 values of 1.1 μM and 35 μM, respectively. The rises in cytosolic sodium ([Na + ] i ) and [Ca 2+ ] i induced by the Na + channel activator veratridine were also inhibited by amitriptyline with IC 50 values of 7 μM and 30 μM, respectively. These results suggest that amitriptyline at micromolar concentrations inhibits both voltage‐sensitive calcium (VSCCs) and sodium channels (VSSCs). Furthermore, submicromolar concentrations of amitriptyline significantly inhibited DMPP‐induced [ 3 H]NE secretion and [Ca 2+ ] i rise, but not veratridine‐ or 70 mM K + ‐induced responses, suggesting that nicotinic acetylcholine receptors (nAChR) as well as VSCCs and VSSCs can be targeted by amitriptyline. DMPP‐induced [Na + ] i rise was much more sensitive to amitriptyline than the veratridine‐induced rise, suggesting that the influx of Na + and Ca 2+ through the nAChR itself is blocked by amitriptyline. Receptor binding competition analysis showed that binding of [ 3 H]nicotine to chromaffin cells was significantly affected by amitriptyline at submicromolar concentrations. The data suggest that amitriptyline inhibits catecholamine secretion by blocking nAChR, VSSC, and VSCC. Synapse 29:248–256, 1998. © 1998 Wiley‐Liss, Inc.