Evidence for cooperative binding of (-)isoproterenol to rat brain β1-adrenergic receptors

In the present study, the effects of the thiol oxidising agent diamide upon the properties of rat brain beta(1)-adrenergic and human platelet serotonin(2A) receptor recognition sites have been investigated using [H-3](-)CGP-12177 (in the presence of ICI-118551) and [3H]LSD as ligands, (-)Isoprenaline inhibited [H-3](-)CGP-12177 binding with n(H) values of 0.87, 0.67, and 0.56 for added Mg2+ concentrations of 0, 2.5, and 25 mM, respectively, Pretreatment with diamide increased the n(H) to above unity for the inhibition of the binding by (-)isoprenaline, without a concomitant effect on the inhibition of the binding by (-)propranolol. In contrast, diamide reduced the affinity of human platelet serotonin(2A)-receptors for antagonists, but did not consistently induce nH values above unity for the inhibition of antagonist binding by serotonin, These results suggest that cooperative interactions reported for cardiac muscarinic receptors may also occur for beta(1)-adrenergic receptors in the rat brain. (C) 1999 Academic Press.