CHARACTERIZATION OF HIGH-AFFINITY BETA-2-ADRENERGIC RECEPTOR-BINDING OF (DIHYDROALPRENOLOL-H-3 TO HUMAN POLYMORPHONUCLEAR CELL PARTICULATES

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  • 1 January 1978
    • journal article
    • research article
    • Vol. 92  (4) , 613-618
Abstract
Human PMN [polymorphonuclear cells] have well-described responses to .beta.-adrenergic catecholamines. These include elevation of cellular levels of cyclic AMP and inhibition of the release of lysosomal contents. Using the radioactive .beta.-adrenergic antagonist (-)-[3H]DHA [dihydroalprenol] in direct ligand-binding studies, .beta.-adrenergic receptors were identified and characterized on particulate preparations of PMN. These particulates bound DHA rapidly (t1/2 [half-time] < 1 min) and reversibly (t1/2 = 8-9 min). DHA binding was saturable and of high affinity (dissociation constant = 1-5 nM) and low capacity (870 .+-. 128 receptors/cell) to a single class of binding sites. Competition for DHA binding sites by .beta.-adrenergic agonists and antagonists was stereoselective [(-)-isomers more potent than (+)-isomers]. The rank order of potency of adrenergic agents in such competition studies indicates that these receptors were of the .beta.2 type. Since PMN can be obtained in high purity with relative ease, the combined use of pharmacologic and ligand-binding studies in PMN provide a useful system for studying .beta.-adrenergic receptors and their function in human subjects.