Evidence for cooperative binding of (-)isoproterenol to rat brain beta(1)-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 serotoni n(2A) receptor recognition sites have been investigated using [H-3](-)CGP-1 2177 (in the presence of ICI-118551) and [3H]LSD as ligands, (-)Isoprenalin e 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, Pretr eatment with diamide increased the n(H) to above unity for the inhibition o f the binding by (-)isoprenaline, without a concomitant effect on the inhib ition of the binding by (-)propranolol. In contrast, diamide reduced the af finity of human platelet serotonin(2A)-receptors for antagonists, but did n ot consistently induce nH values above unity for the inhibition of antagoni st binding by serotonin, These results suggest that cooperative interaction s reported for cardiac muscarinic receptors may also occur for beta(1)-adre nergic receptors in the rat brain. (C) 1999 Academic Press.