(−)-[ 125I]Pindolol binding to the human platelet β-adrenoceptor: Characterisation and agonist interactions

Abstract

The binding of (−)-[ 125I]pindolol ((−)-[ 125I]PIN) to human platelet membranes has been examined and identifies a relatively low density of β-adrenoceptor binding sites in this tissue. The relative order of potency of the catecholamines in displacement experiments, isoprenaline > adrenaline > noradrenaline and curve-fitting analysis of the competition binding isotherms using subtype selective β-adrenergic antagonists, suggest the presence of an homogeneous population of β 2-adrenoceptors. The effects of guanine nucleotides and mono- and divalent cations on the isoprenaline displacement of (−)-[ 125I]PIN binding to human platelet and rat lung membrane β-adrenoceptors was compared in parallel experiments. In the presence of Mg 2+ the agonist showed relatively lower overall affinity for the platelet receptor with a steep displacement curve, Hill slope approaching unity. Under these circumstances Gpp(NH)p characteristically produced a shift to the right and a steepening of the agonist displacement curve in rat lung but had no effect in platelet membranes. NaCl caused a parallel shift to the right of the curves in both systems in the presence or absence of Gpp(NH)p. The significance of these results of these results in relationship to the efficiency of coupling of the human platelet β-adrenoceptor to adenylate cyclase is discussed.