Multiple effects of cocaine upon evoked secretion in bovine adrenal medullary chromaffin cells: additional insight into the mechanism of action of cardiac glycosides

• Published in: Naunyn-Schmiedeberg's archives of pharmacology Vol. 339; no. 3; pp. 272 - 280
• Main Authors: POWIS, D. A, O'BRIEN, K. J, TOROK, T. L
• Format: Journal Article
• Language: English
• Published: Heidelberg Springer 01-03-1989; Berlin; New York, NY
• Subjects: Adrenal Medulla - cytology; Adrenal Medulla - drug effects; Anesthetics. Neuromuscular blocking agents; Animals; Biological and medical sciences; Carbachol - pharmacology; Cardiac Glycosides - pharmacology; Catecholamines - metabolism; Cattle; Chromaffin System - cytology; Chromaffin System - drug effects; Cocaine - pharmacology; Culture Media; Desipramine - pharmacology; In Vitro Techniques; Medical sciences; Neuropharmacology; Ouabain - pharmacology; Pharmacology. Drug treatments; Rubidium Radioisotopes; Sodium - metabolism; Tetrodotoxin - pharmacology; Veratridine - pharmacology; Cell culture; Cardiotonic agent; Bovine; Digitalis; Adrenal medulla; Glucoside; Ionic channel; Catecholamine; Chromaffin cell; Biological activity; Uptake; Local anesthetic; Vertebrata; Mammalia; Sodium; Neurotransmitter; Cocaine; Norepinephrine; Artiodactyla; Mechanism of action; Ungulata
• ISSN: 0028-1298; 1432-1912
• DOI: 10.1007/BF00173577

Experiments to determine the effects of the catecholamine neuronal uptake blockers cocaine and desipramine, and of the cardiac glycoside, ouabain, upon 3H-(noradrenaline) efflux have been performed with bovine adrenal medullary chromaffin cells in tissue culture. Both cocaine and desipramine reduced 3H-noradrenaline uptake into chromaffin cells. Inhibitable uptake was 80% of total accumulation over 60 min; this degree of inhibition was produced by cocaine (30 mumol/l) or desipramine (1 mumol/l). Cocaine (30 mumol/l) had no effect upon spontaneous 3H-efflux measured over 60 min, but reduced that evoked over the same period by carbachol (EC50), veratridine (EC50) and by ouabain (100 mumol/l). Cocaine did not reduce that efflux evoked by raised levels of K+ (28 mmol/l; EC50). Desipramine (1 mumol/l), like cocaine, had no effect upon spontaneous efflux of 3H, but reduced that efflux evoked by carbachol, veratridine and ouabain. Tetrodotoxin (TTX) inhibited veratridine-evoked 3H efflux (IC50 0.2 mumol/l). The degree of inhibition caused by TTX (0.2 mumol/l) was not increased by cocaine (30 mumol/l). TTX also inhibited ouabain-evoked 3H efflux: this was reduced by 55% by a concentration of TTX (1 mumol/l) sufficient to virtually abolish veratridine-evoked efflux. Cocaine (30 mumol/l) in the presence of TTX (1 mumol/l) did not further inhibit ouabain-evoked efflux. Cocaine (30 mumol/l) did not alter 86Rb+ uptake into chromaffin cells, nor did it alter that inhibition of 86Rb+ uptake produced by ouabain (100 mumol/l) indicating that cocaine has no effect upon Na,K-ATPase activity.