Effects of dopamine on ATP-sensitive potassium channels in porcine coronary artery smooth-muscle cells.
BACKGROUND
Dopamine is reported to be a coronary vasodilator; however, the exact mechanism of dopamine action in the coronary circulation remains unclear. In this study, we hypothesized that dopamine-induced activation of coronary ATP-sensitive potassium (KATP) channels may be associated with coronary vasodilation. We therefore investigated the direct effects of dopamine on coronary KATP-channel activity.


METHODS
We used patch-clamp configurations to investigate the effects of dopamine on coronary KATP-channel activity.


RESULTS
Application of dopamine (10 to 10 M) to the bath solution during cell-attached recordings induced a concentration-dependent increase in KATP-channel activity. In contrast, dopamine failed to activate KATP channels in inside-out patches. Dopamine-induced coronary KATP-channel currents in cell-attached patches were inhibited by pretreatment with the selective D1-like antagonist, Sch-23390, but they were not influenced by the selective D2-like antagonist, domperidone, or the beta-adrenergic receptor antagonist, propranolol. The selective D1-like agonist, SKF-38393, and the adenylyl cyclase activator, forskolin, mimicked the dopamine effects on coronary KATP channels. Furthermore, pretreatment with an inhibitor of protein kinase A, Rp-cAMPS, abolished the dopamine-induced KATP-channel activation.


CONCLUSIONS
This study demonstrates that dopamine activates coronary KATP channels via signal transduction involving the D1-like dopaminergic receptor-protein kinase A-signaling pathway.
Kawano
Hiroaki
H
Department of Anesthesiology, Tokushima University School of Medicine, Tokushima, Japan. hir.kawa@clin.med.tokushima-u.ac.jp
Kawano
Takashi
T
Tanaka
Katsuya
K
Eguchi
Satoru
S
Takahashi
Akira
A
Nakaya
Yutaka
Y
Oshita
Shuzo
S
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D003331:Coronary Vessels / Q000166:cytology*; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D004294:Domperidone / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D054086:KATP Channels / Q000819:agonists* / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D011433:Propranolol / Q000494:pharmacology; D017447:Receptors, Dopamine D1 / Q000502:physiology; D015398:Signal Transduction; D013552:Swine; D013873:Thionucleotides / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D001552:Benzazepines; D002316:Cardiotonic Agents; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D054086:KATP Channels; D017447:Receptors, Dopamine D1; D013873:Thionucleotides; D014665:Vasodilator Agents; D005576:Colforsin; C016957:adenosine-3',5'-cyclic phosphorothioate; D004294:Domperidone; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D011433:Propranolol; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D004298:Dopamine