Dopamine inhibits a sustained calcium current through activation of alpha adrenergic receptors and a GTP-binding protein in adult rat sympathetic neurons.
Although it is suspected that dopamine (DA) inhibits a Ca++ current in sympathetic neurons, the receptor and the Ca++ channel type involved are still unknown. We found that DA caused a reversible inhibition on omega-conotoxin sensitive and resistant Ca++ currents in the superior cervical ganglion (SCG). The concentration of DA that induced half-maximal inhibition was 3.0 microM. The DA receptor agonists (+/-)-SKF-38393 (D1 type) and quinpirole (D2 type) appeared unable to induce an inhibition of the Ca++ current. Furthermore, the receptor antagonists SCH-23390 (D1 type) and (-)-sulpiride (D2 type) did not prevent the inhibitory effect of DA. This suggests that the effect of DA on the Ca++ current was not due to activation of DA receptors. The inhibition of the Ca2++ current by DA was reduced by application of 1 microM phentolamine, a nonselective alpha adrenergic antagonist, and by prazosin and yohimbine, alpha-1 and alpha-2 receptor antagonists, respectively. The beta adrenergic receptor antagonist propranolol did not block the effect of DA. A guanine nucleotide-binding protein appears to be involved in the activation of adrenergic receptors by DA. The addition of GTP-gamma-S (0.1 mM) to the intracellular solution produced an effect similar to that of DA. Incubation of sympathetic neurons with pertussis toxin reduced the effect of DA by 90%. The results indicate that DA reduces the number of available Ca++ channels in sympathetic neurons by activation of alpha adrenergic receptors, which are associated with a pertussis-sensitive GTP-binding protein.
Aguayo
L G
LG
Section of Electrophysiology, National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland.
Grossie
J
J
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000494:pharmacology; D008024:Ligands; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000378:metabolism
D002121:Calcium Channel Blockers; D008024:Ligands; D011942:Receptors, Adrenergic, alpha; D017448:Receptors, Dopamine D2; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D002118:Calcium; D004298:Dopamine