Solubilization of human platelet alpha-adrenergic receptors: evidence that agonist occupancy of the receptor stabilizes receptor--effector interactions.

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Abstract
The .alpha.-adrenergic receptors of human platelet membranes can be directly identified by both a radiolabeled agonist, [3H]epinephrine, and a radiolabeled antagonist, [3H]yohimbine. Digitonin solubilizes a binding component from the membrane that is indistinguishable from the .alpha.-receptor identified in the native platelet membrane; this was assessed by order of potency of agonists and antagonists, and of affinity of the receptor for [3H]-yohimbine and competing antagonists. The solubilized receptor demonstrates a reduced affinity for agonists and a loss of the ability of guanine nucleotides to modulate receptor affinity for agonists. Prelabeling of human platelet membranes with [3H]-epinephrine causes a guanine nucleotide-sensitive agonist-receptor complex that sediments more rapidly in sucrose gradients than do unoccupied or antagonist-occupied receptors. Agonist occupancy of the .alpha.-receptor prior to membrane solubilization may promote or stabilize receptor interaction with effector components in the membrane, 1 of which may be the GTP regulatory protein responsible for modulation of receptor affinity.