SUMMARY1. 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-phenylpiperazinium 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 ofGDP-,-S in the pipette internal solution did not affect apomorphinedependent inhibition of nicotinic-evoked responses, while the decrease in whole-cell Ca2`current induced by apomorphine was completely inhibited in the presence of GDP-fl-S.

SUMMARY1. The effects of cholinergic agonists on voltage-dependent calcium current (ICa) were studied in cultured chromaffin cells from bovine adrenal medulla.2. Application of both acetylcholine (ACh) and nicotine resulted in inward nicotinic current from a holding potential of -90 mV, and at the same time reversible decreases in depolarization-activated ICa. Both of these effects were blocked by d-tubocurarine, while atropine pre-treatment was ineffective.3. Internal accumulation of neither Na+ nor Ca2+ seems likely to explain the nicotinic-agonist-dependent decrease in ICa, as the modulation was observed with symmetrical Na+ solutions, with Ca2+-free Ba2+-containing external solutions, from holding potentials of both -90 and -40 mV, and when the internal Ca2+ buffer capacity was increased. 4. Isodihydrohistrionicotoxin, an open-channel blocker which does not compete for the agonist binding site, completely inhibited inward cholinergic currents while the agonist-dependent decrease in ICa was seen in only two of fifteen cells.5. The nicotinic agonist-mediated decreases in Icawere not voltage-dependent. 6. No changes in voltage-dependent INa were seen with the nicotinic agonists. 7. Muscarine, with or without GTP in the pipette solution, produced neither modulation of ICa nor any changes in steady holding currents. The nicotinic current and the reversible decrease in ICa induced by ACh and nicotine were not affected by including GTP, or the guanine nucleotide analogues GDP-/1-S and GTP-y-S, in the pipette solution.8. A 10 min pre-incubation of the cells in a high-K+ solution optimal for catecholamine secretion did not affect the nicotinic agonist-mediated decreases in

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