MODULATION OF SECRETION BY DOPAMINE INVOLVES DECREASES IN CALCIUM AND NICOTINIC CURRENTS IN BOVINE CHROMAFFIN CELLS

1. Catecholamine secretion from cultured bovine adrenal chromaffin cells was decreased in a dose‐dependent manner by the D2 dopamine agonists apomorphine and LY 17 1555. 2. 45Ca2+ uptake was similarly inhibited and whole‐cell Ca2+ currents were reduced by apomorphine. 3. These inhibitory effects of D2 agonists depended on the secretagogue used, being much more pronounced for nicotine‐evoked responses compared to high K+ stimulation, indicating another possible site of action of apomorphine up‐stream of Ca2+ entry. 4. Inhibition by apomorphine of nicotine‐evoked responses could not be explained by competitive antagonism against nicotine or DMPP (1,1‐dimethyl‐4‐phenyl‐piperazinium iodide). 5. Apomorphine caused reductions of inward whole‐cell nicotinic current evoked by ACh and nicotine. 6. Inhibition of nicotine‐evoked secretion and 22Na+ influx by apomorphine were not affected by tetrodotoxin, and voltage‐dependent, whole‐cell Na+ currents were unaltered by apomorphine. 7. No evidence was obtained for increases in K+ conductance by apomorphine. 8. Action potentials recorded in whole‐cell current clamp were blocked by apomorphine when they were triggered by nicotinic depolarization but not when they were elicited by direct electrical stimulation. 9. Inclusion of GDP‐beta‐S in the pipette internal solution did not affect apomorphine‐dependent inhibition of nicotinic‐evoked responses, while the decrease in whole‐cell Ca2+ current induced by apomorphine was completely inhibited in the presence of GDP‐beta‐S. 10. Increases in cyclic AMP caused by cholera toxin and forskolin did not change the apomorphine‐dependent inhibitory effects on nicotine‐evoked secretion, indicating that changes in cyclic AMP levels caused by dopamine receptor stimulation are probably not involved. © 1990 The Physiological Society