Robert J. Lefkowitz

TL;DR: Agonist competition curves with [3H]dihydroergocryptine at eht human platelet's alpha 2-receptor may be resolved into two affinity components, interconvertible by guanine nucleotides, suggesting the agonist-promoted association of the alpha 2 -receptor with an additional membrane component.

TL;DR: It is concluded that in vitro [ 3 H]norepinephrine binding is unrelated to microsomal catechol-o-methyl transferase.

Abstract: Exposure of certain cells (e.g., frog erythrocytes) to beta adrenergic agonists leads to desensitization of the membrane-bound adenylate cyclase to further beta adrenergic stimulation, which is associated with a fall in the number of beta adrenergic receptor binding sites. To explain further the mechanism of this agonist-induced desensitization of adenylate cyclase-coupled beta adrenengic receptors, intact frog erythrocytes were "desensitized" by incubation with the radiolabeled beta adrenergic agonist [ 3 H]hydroxybenzylisoproterenol. This incubation with agonist led to a "loss" of 33% of the (-)-[ 3 H]dihydroalprenolol binding sites ( beta adrenergic receptors) from membrane fractions prepared from the erythrocytes. Although 192 fmoles/mg of protein of (-)-[ 3 H]dihydroalprenolol binding sites were lost from the membranes of desensitized cells, only 24 fmoles/mg of protein of [ 3 H]hydroxybenzylisoproterenol remained specifically bound to sites in the membranes from the desensitized cells. Thus residual agonist, tightly bound to "high-affinity" receptor sites, does not explain the loss of beta adrenergic receptor binding sites that occurs during desensitization of the intact cells.

TL;DR: The beta 1- and beta 2-adrenergic receptor subtypes are biochemically and functionally similar, because both receptors mediate the catecholamine-dependent activation of adenylate cyclase through the GTP-binding protein, Gs.