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.
Sontag
J M
JM
Groupe de Neurobiologie Structurale et Fonctionnelle, Unité INSERM U44, Strasbourg, France.
Sanderson
P
P
Klepper
M
M
Aunis
D
D
Takeda
K
K
Bader
M F
MF
D000200:Action Potentials / Q000187:drug effects; D000313:Adrenal Medulla / Q000378:metabolism*; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002417:Cattle; D002478:Cells, Cultured; D004298:Dopamine / Q000502:physiology*; D004594:Electrophysiology; D019204:GTP-Binding Proteins / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000502:physiology*; D015222:Sodium Channels / Q000187:drug effects
D015220:Calcium Channels; D015221:Potassium Channels; D011978:Receptors, Nicotinic; D015222:Sodium Channels; D019204:GTP-Binding Proteins; D001058:Apomorphine; D004298:Dopamine; D009638:Norepinephrine