Endogenous noradrenaline masks beta-adrenergic receptors in rat heart membranes via tight agonist binding.

The tight binding of noradrenaline (NA) to beta-adrenergic receptors was studied in membranes from the left ventricular myocardium of the rat. Addition of GTP (0.1 mM) to membrane preparations from control rats (NA concentration 8.5 +/- 2.1 nM) caused a 4-35% (N = 8) increase (P less than 0.01) in the number of specific binding sites of 125Ipindolol. In contrast, addition of GTP did not cause any changes in the number of beta-adrenergic receptors in heart membranes from reserpinized animals (NA concentration less than 0.1 nM). In heart membranes from reserpinized animals, preincubation with NA (followed by washing) revealed a time- and concentration-dependent decrease with a maximum of 35-40% in the 125Ipindolol-binding sites. This agonist-mediated decrease in the number of receptors was prevented if GTP was also present in the NA-preincubation medium. It is concluded that NA can undergo tight binding to beta-adrenergic receptors in rat heart membranes. The heart-membrane preparations contain endogenous NA which, via tight agonist binding, is responsible for masking part of the beta-adrenergic receptor population.