COEXISTENCE OF FUNCTIONING BETA(1)-ADRENOCEPTOR AND BETA(2)-ADRENOCEPTOR IN SINGLE MYOCYTES FROM HUMAN VENTRICLE

Background. Both beta1- and beta2-adrenoceptors (beta1AR and beta2AR) are present in human ventricle. This study was designed to determine w hether the two subtypes contribute to contraction in single myocytes f rom human heart. Methods and Results. (-)-Epinephrine increased the co ntraction amplitude and velocity of single myocytes isolated from the ventricles of failing and nonfailing human hearts. Concentration-respo nse curves to (-)-epinephrine were constructed in the presence and abs ence of selective antagonists for beta1AR (CGP 20712A) and beta2AR (IC I 118,551). Responses to (-)-epinephrine were antagonized to a variabl e degree by the blockers, suggesting heterogeneous contribution of bet a1AR and beta2AR among cells. The most common response in single myocy tes was that ICI 118,551 (50 nmol/L) shifted the concentration-respons e curve less than 10-fold: this was lower than the 100-fold shift expe cted for a pure beta2AR effect. Inclusion of CGP 20712A (300 nmol/L) w ith ICI 118,551 shifted the (-)-epinephrine curve still further. These observations suggest that both beta1AR and beta2AR contribute to the increase in contraction amplitude with (-)-epinephrine in this group o f myocytes. When 300 nmol/L CGP 20712A was present as the sole antagon ist, only a marginal shift of the concentration-response curve for (-) -epinephrine was usually observed, indicating that beta1AR were not me diating the effect of these low concentrations of (-)-epinephrine. Bot h beta1AR and beta2AR mediated a considerable abbreviation of the time to peak contraction and time to 50% relaxation in the single cells. C onclusions. beta1AR and beta2AR coexist and function on human ventricu lar myocytes. At low (-)-epinephrine concentrations, contractile respo nses are predominantly mediated by beta2AR rather than beta1AR in myoc ytes from failing hearts.