Multiple Effects of Cocaine Upon Evoked Secretion in Bovine Adrenal Medullary Chromaffin Cells. Additional Insight into the Mechanism of Action of Cardiac Glycosides

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.(ABSTRACT TRUNCATED AT 250 WORDS)