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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T J ParkK T Kim

Abstract

We investigated the effects of amitriptyline, a tricyclic antidepressant, on [3H]norepinephrine ([3H]NE) secretion and ion flux in bovine adrenal chromaffin cells. Amitriptyline inhibited [3H]NE secretion induced by 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP) and 70 mM K+. The half maximal inhibitory concentration (IC50) was 2 microM and 9 microM, respectively. Amitriptyline also inhibited the elevation of cytosolic calcium ([Ca2+]i) induced by DMPP and 70 mM K+ with IC50 values of 1.1 microM and 35 microM, 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 microM and 30 microM, 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 [3H]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 t...Continue Reading

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Citations

Oct 6, 2007·Molecular Neurobiology·Gerhard Rammes, Rainer Rupprecht
Dec 11, 2002·Biochemical Pharmacology·Tae-Ju ParkKyong-Tai Kim
Mar 18, 2003·Cellular Signalling·Tae-Ju Park, Kyong-Tai Kim
Sep 17, 2009·Drug Development and Industrial Pharmacy·Sejal PatelGrazia Stagni
Mar 30, 2006·The Kaohsiung Journal of Medical Sciences·Bor-Chin ChengChin-Chen Chu
Sep 13, 2003·Kidney International·Eduardo AcharNestor Schor
May 22, 2007·The Journal of Pain : Official Journal of the American Pain Society·Peter FridrichPeter Gerner
Jun 17, 2011·Pain Practice : the Official Journal of World Institute of Pain·David J Kopsky, Jan M Keppel Hesselink
Mar 29, 2001·Biochemical Pharmacology·T J ParkK T Kim
Mar 8, 2006·The International Journal of Biochemistry & Cell Biology·Hugo R AriasCecilia Bouzat
Jul 19, 2002·Rheumatic Diseases Clinics of North America·Srinivas G Rao
Nov 12, 2003·Biochemical Pharmacology·Eiichi TachikawaJon M Lindstrom
Oct 25, 2002·The Journal of Pharmacy and Pharmacology·Florentina PenaMaria-Luisa Flonta
Nov 4, 2000·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·K S OhK T Kim
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Apr 15, 2000·Pharmacology, Biochemistry, and Behavior·S S SchiffmanL Iuga

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