Post-natal evolution of rat cardiac beta-adrenoceptors.

Cardiac beta-adrenoceptors (beta AR) were studied using membranes prepared at birth (day 0) and at days 7, 10, 15, 21, 30, 45 and 60. Saturation experiments using the antagonist ligand (125I)-iodocyanopindolol (ICYP) allowed the determination of beta AR number (Bmax) and ICYP dissociation constant (Kd), while (-)isoproterenol competition curves of ICYP binding, performed in the absence or presence of Gpp(NH)p (10(-4) M), were used to measure the relative proportions of high and low affinity states of the beta AR for the agonist and to assess the ability of beta AR to couple with the GTP-binding protein. Rat cardiac beta AR evolved at 3 distinct periods: during the first period (days 0-10), the receptor density and ICYP Kd were half that of adults, and beta AR were present only in an homogeneous high affinity state. The second period (days 15-21) was characterized by a progressive increase in beta AR number and ICYP Kd, while analysis of (-)isoproterenol competition curves indicated that beta AR were poorly coupled to the GTP-binding protein. In the third period (days 30-60), ICYP Bmax and Kd were respectively 53.9 +/- 1.2 fmoles/mg protein and 106.4 +/- 2.9 pM, while analysis of (-)isoproterenol competition curves showed the existence of high and low affinity binding states in equal proportions in the absence of Gpp(NH)p, and of one homologous low affinity state of the receptor in its presence. These data indicate that beta AR follow a postnatal evolution marked by an increase in beta AR density concomitant with a decrease in affinity toward the antagonist ligand ICYP, accompanied by the progressive appearance of a poorly-coupled beta AR. However, the number of efficiently coupled receptors was found to be similar in adult and newborn rats.