Beta-adrenergic receptor interaction with guanosine triphosphate in fetal rabbit myocardial membranes

To investigate whether, in developing fetal rabbit myocardium, the affinity of beta-adrenoreceptors (beta-AR) for beta-AR agonists is regulated by guanosine triphosphate (GTP), we performed in vitro competition experiments utilizing 125I-hydroxybenzylpindolol (I-HYP), a beta-AR antagonist, as the radioligand, and l-isoproterenol (l-I) and l-propranolol (l-P), as beta-AR agonist and antagonist, respectively. At gestational ages from 21 to 31 days (term 31 days), in the presence of GTP, there was a 4-fold increase in the KI for the inhibition of specific I-HYP binding by l-I but not by l-P. Moreover, in the presence of GTP, there was a significant shift of the Hill coefficient to values closer to 1 only in the case of l-I. We conclude that: (1) beta-AR can form a 'high affinity' complex with l-I in the absence of GTP, detectable from days 21 to 31 of gestation; (2) the conversion of the former to a 'low affinity' state appears to be a GTP-dependent process.