AMPHETAMINE-INDUCED EXOCYTOSIS OF CATECHOLAMINES FROM THE COW ADRENAL MEDULLA

¹ Department of Pharmacology, University of Colorado School of Medicine, Denver, Colorado

Exposure of perfused isolated cow adrenal glands to d-amphetamine in concentrations between 1.8 x 10^-5 and 1.8 x 10^-2 M caused a dose-related secretion of catecholamines. protein and dopamine--hydroxylase activity. At 5.4 x 10^-3 M amphetamine, adenine nucleotides, chromogranin antigen and acid deoxyribonuclease activity were released, and the secretion pattern observed at this concentration is qualitatively similar to that for carbachol. At concentrations of amphetamine less than 5.4 x 10^-3 M, catecholamine release was dependent upon the presence of calcium in the perfusion fluid; at higher concentrations there was partial inhibition of release by removal of calcium from the perfusion fluid. When calcium was omitted from the medium, the uptake of amphetamine by chopped preparations of adrenal medulla was reduced 18 to 27%, although diffusion of catecholamines out of the tissue was not affected by calcium deletion. In concentrations higher than 10^-3 M, d-amphetamine released catecholamine from isolated cow adrenal medulla chromaffin granules. It is concluded that amphetamine releases catecholamines from chromaffin tissue by both exocytosis and by direct interaction with chromaffin granules and that catecholamine release by exocytosis predominates at lower concentrations of amphetamine.