Activation of facilitation calcium channels in chromaffin cells by D1 dopamine receptors through a cAMP/protein kinase A-dependent mechanism.
Facilitation calcium channels in unstimulated bovine chromaffin cells are normally quiescent but are activated by large pre-depolarizations or by repetitive depolarization in the physiological range. The activation of these 27-pS dihydropyridine-sensitive channels by repetitive stimulation, such as by increased splanchnic nerve activity, can lead to an almost twofold increase in Ca2+ current in these cells. This increase in Ca2+ current is of probable physiological importance in stimulating rapid catecholamine secretion in response to danger or stress. We have identified D1 dopaminergic receptors on bovine chromaffin cells by fluorescence microscopy. Here we show that stimulation of the D1 receptors activates the facilitation Ca2+ currents in the absence of pre-depolarizations or repetitive activity, and that activation by D1 agonists is mediated by cyclic AMP and protein kinase A. The recruitment of facilitation Ca2+ channels by dopamine may form the basis of a positive feedback loop mechanism for catecholamine secretion.
Artalejo
C R
CR
University of Chicago, Department of Pharmacological and Physiological Sciences, Illinois.
Ariano
M A
MA
Perlman
R L
RL
Fox
A P
AP
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000311:Adrenal Glands / Q000166:cytology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002417:Cattle; D002838:Chromaffin System / Q000502:physiology*; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology*; D004298:Dopamine / Q000502:physiology; D004553:Electric Conductivity; D004558:Electric Stimulation; D008856:Microscopy, Fluorescence; D015737:Nisoldipine / Q000494:pharmacology; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D011954:Receptors, Dopamine / Q000502:physiology*; D017447:Receptors, Dopamine D1; D013873:Thionucleotides / Q000494:pharmacology
D001552:Benzazepines; D015220:Calcium Channels; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D013873:Thionucleotides; D015124:8-Bromo Cyclic Adenosine Monophosphate; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; D015737:Nisoldipine; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000242:Cyclic AMP; D011494:Protein Kinases; D001058:Apomorphine; D004298:Dopamine