Effects of dopexamine hydrochloride on calcium channels in isolated guinea pig ventricular myocytes.
The mechanisms responsible for the cardiac positive inotropic effects of dopexamine hydrochloride, a combined dopamine receptor agonist at both D1-receptors and beta 2-adrenoceptors, were studied. The calcium channel currents were recorded using whole-cell patch clamp technique in isolated guinea pig ventricular myocytes. At a holding potential of -40 mV, cells were depolarized to 0 mV for 400 ms at a frequency of 0.2 Hz. Dopexamine hydrochloride at doses of 5, 50 and 100 microM increased the verapamil-sensitive Ca2+ inward current by 109, 147 and 194%, respectively. The effects of dopexamine hydrochloride on Ca2+ current reached its maximum at 5 min and partially recovered after washout of the drugs. The increased Ca2+ current induced by dopexamine hydrochloride was completely inhibited by 20 microM propranolol, a beta-adrenoceptor antagonist, and was not antagonized by 20 microM of SCH23390, a highly selective D1-receptor antagonist. These results suggest that the cardiac positive inotropic effects of dopexamine hydrochloride are brought about by the increase of Ca2+ current via stimulation of beta 2-adrenoceptors.
Department of Physiology, Shanxi Medical University, Taiyuan, China.
W
W
Dun
R R
RR
Zhao
Y
Y
Liang
B W
BW
Wu
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects*; D004298:Dopamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000166:cytology*; D018408:Patch-Clamp Techniques; D011433:Propranolol / Q000494:pharmacology; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D001552:Benzazepines; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D018343:Receptors, Adrenergic, beta-2; C046318:dopexamine; D011433:Propranolol; D014700:Verapamil; D004298:Dopamine