title: Multiple effects of cocaine upon evoked secretion in bovine adrenal medullary chromaffin cells. Additional insight into the mechanism of action of cardiac glycosides.
abstract: 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)
authors.affiliation: Neuroscience Group, Faculty of Medicine, University of Newcastle, NSW, Australia.
authors.forename: D A
authors.initials: DA
authors.lastname: Powis
authors.forename: K J
authors.initials: KJ
authors.lastname: O'Brien
authors.forename: T L
authors.initials: TL
authors.lastname: Török
mesh_terms: D000313:Adrenal Medulla / Q000166:cytology / Q000187:drug effects*; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002301:Cardiac Glycosides / Q000494:pharmacology*; D002395:Catecholamines / Q000378:metabolism; D002417:Cattle; D002838:Chromaffin System / Q000166:cytology / Q000187:drug effects*; D003042:Cocaine / Q000494:pharmacology*; D003470:Culture Media; D003891:Desipramine / Q000494:pharmacology; D066298:In Vitro Techniques; D010042:Ouabain / Q000494:pharmacology; D012414:Rubidium Radioisotopes; D012964:Sodium / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology
chemical_list: D002301:Cardiac Glycosides; D002395:Catecholamines; D003470:Culture Media; D012414:Rubidium Radioisotopes; D013779:Tetrodotoxin; D010042:Ouabain; D014701:Veratridine; D002217:Carbachol; D012964:Sodium; D003042:Cocaine; D003891:Desipramine