Differential inhibition of catecholamine secretion by amitriptyline through blockage of nicotinic receptors, sodium channels, and calcium channels in bovine adrenal chromaffin cells
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- Title
- Differential inhibition of catecholamine secretion by amitriptyline through blockage of nicotinic receptors, sodium channels, and calcium channels in bovine adrenal chromaffin cells
- Authors
- Park, TJ; Shin, SY; Suh, BC; Suh, EK; Lee, IS; Kim, YS; Kim, KT
- Date Issued
- 1998-07
- Publisher
- WILEY-LISS
- Abstract
- We investigated the effects of amitriptyline, a tricyclic antidepressant, on [H-3]norepinephrine ([H-3]NE) secretion and ion flux in bovine adrenal chromaffin cells. amitriptyline inhibited [H-3]NE secretion induced by 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP) and 70 mM K+. The half maximal inhibitory concentration (IC50) was 2 mu M and 9 mu M, respectively. Amitriptyline also inhibited the elevation of cytosolic calcium ([Ca2+](i)) induced by DMPP and 70 mM K+ with IC50 values of 1.1 mu M and 35 mu M, respectively. The rises in cytosolic sodium ([Na+](i)) and [Ca2+](i) induced by the Na+ channel activator veratridine were also inhibited by amitriptyline with IC50 values of 7 mu M and 30 mu M, 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 [H-3]NE secretion and [Ca2+](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 Ca2+ through the nAChR itself is blocked by amitriptyline. Receptor binding competition analysis showed that binding of [H-3]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. (C) 1998 Wiley-Liss, Inc.
- Keywords
- amitriptyline; catecholamine secretion; nicotinic receptor; calcium channel; sodium channel; RAT FRONTAL-CORTEX; ANTIDEPRESSANT DRUGS; ACETYLCHOLINE-RECEPTOR; TYROSINE-HYDROXYLASE; LOCUS-CERULEUS; MESSENGER-RNA; PC12 CELLS; NEURONS; ANTAGONISTS; BINDING
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/20762
- DOI
- 10.1002/(SICI)1098-2396(199807)29:3<248::AID-SYN7>3.3.CO;2-A
- ISSN
- 0887-4476
- Article Type
- Article
- Citation
- SYNAPSE, vol. 29, no. 3, page. 248 - 256, 1998-07
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