Effects of dopexamine hydrochloride on calcium channels in isolated guinea pig ventricular myocytes.

ABSTRACT

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.