Dopamine receptors on adrenal chromaffin cells modulate calcium uptake and catecholamine release.
The presence of dopamine-containing cells in sympathetic ganglia, i.e., small, intensely fluorescent cells, has been known for some time. However, the role of dopamine as a peripheral neurotransmitter and its mechanism of action are not well understood. Previous studies have demonstrated the presence of D2 dopamine receptors on the surface of bovine adrenal chromaffin cells using radioligand binding methods and dopamine receptor inhibition of catecholamine release from perfused adrenal glands. In the present study, we provide evidence confirming a role of dopamine receptors as inhibitory modulators of adrenal catecholamine release from bovine chromaffin cell cultures and further show that the mechanism of modulation involves inhibition of stimulated calcium uptake. Apomorphine gave a dose-dependent inhibition (IC50 = 1 microM) of 45Ca2+ uptake stimulated by either nicotine (10 microM) or membrane depolarization with an elevated K+ level (60 mM). This inhibition was reversed by a series of specific (including stereospecific) dopamine receptor antagonists: haloperidol, spiperone, sulpiride, and (+)-butaclamol, but not (-)-butaclamol. In addition, the calcium channel agonist Bay K 8644 was used to stimulate uptake of 45Ca2+ into chromaffin cells, and this uptake was also inhibited by the dopamine receptor agonist apomorphine. The combined results suggest that dopamine receptors on adrenal chromaffin cells alter Ca2+ channel conductance, which, in turn, modulates catecholamine release.
Bigornia
L
L
Department of Pharmacology and Toxicology, Albany Medical College, New York 12208.
Suozzo
M
M
Ryan
K A
KA
Napp
D
D
Schneider
A S
AS
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000311:Adrenal Glands / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D002069:Butaclamol / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002132:Calcium Radioisotopes; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D002838:Chromaffin System / Q000187:drug effects / Q000378:metabolism*; D004553:Electric Conductivity; D006220:Haloperidol / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology*; D013134:Spiperone / Q000494:pharmacology; D013469:Sulpiride / Q000494:pharmacology
D002132:Calcium Radioisotopes; D002395:Catecholamines; D007473:Ion Channels; D011954:Receptors, Dopamine; D013134:Spiperone; D009538:Nicotine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D013469:Sulpiride; D002069:Butaclamol; D006220:Haloperidol; D001058:Apomorphine; D011188:Potassium; D002118:Calcium