BETA(2)-ADRENERGIC RECEPTOR ACTIONS IN NEONATAL AND ADULT-RAT VENTRICULAR MYOCYTES

The physiological function of beta(2)-adrenergic receptors in the neon atal and adult heart is incompletely understood, and possible age-depe ndent differences in beta(2)-receptor actions have not been considered . We used isoproterenol (mixed beta(1)- and beta(2)-receptor agonist) and zinterol (beta(2)-selective agonist) to compare beta-receptor subt ype actions in neonatal and adult rat ventricular myocytes. When deliv ered as a bolus at a final concentration of 10(-7) mol/L, both isoprot erenol and zinterol increased the amplitude and hastened the kinetics of the calcium and cell-shortening transients in neonatal myocytes. Un der identical experimental conditions, isoproterenol increased the amp litude and accelerated the kinetics of the calcium transient and the t witch in adult myocytes, whereas zinterol did not. In the presence of CGP 20712A (beta(1)-receptor blocker), a 100-fold higher concentration of zinterol increased the amplitude but prolonged the duration of the twitch in adult myocytes. To probe the mechanism for this age-depende nt difference in beta(2)-receptor responsiveness, we compared beta-rec eptor expression and stimulation of cAMP accumulation in neonatal and adult myocytes. beta-Receptor density was per cell in neonatal myocyte s and 186 346+/-13 356 sites per cell in adult myocytes; the relative proportion of beta(2)-receptors was comparable in each (16.7+/-2.3% an d 16.9+/-0.9%, respectively). Isoproterenol induced a large increase i n cAMP accumulation in neonatal and adult myocytes (20.0+/-1.0- and 20 .6+/-2.6-fold over basal). In contrast, zinterol evoked a substantial increase in cAMP accumulation in neonatal myocytes but only a minor in crease in adult myocytes. These studies provide evidence that at low a gonist concentrations, beta(2)-receptor activation contributes to the positive inotropic response by increasing cAMP and increasing the ampl itude and hastening the kinetics of the twitch in neonatal, but not ad ult, myocytes. Moreover, these results suggest that age-dependent diff erences in beta(2)-receptor coupling to more distal elements in the si gnaling cascade can influence myocyte beta(2)-receptor responsiveness.