Solubilization of a mammalian beta-adrenergic receptor.

Naunyn Schmiedebergs Arch Pharmacol, 1978/12;305(3):191-200.

Kleinstein J, Glossmann H, Braun L, Konrad C

PMID: 216931

Impact factor: 3.195

Abstract
Binding sites for iodohydroxybenzylpindolol with characteristics of a beta2-adrenergic receptor have been identified in a crude membrane fraction from guinea-pig lung. The binding sites could be solubilized by treatment of the membrane fraction with digitonin. Upon solubilization receptors retain their beta2-adrenergic type as indicated by the rank order of potencies of agonists in binding-inhibition experiments. The solubilized receptors demonstrate a marked increase in affinity for agonists compared with particulate receptors whereas antagonist affinity remains unchanged. Solubilized receptors are insensitive to divalent cations (Mg2+, Mn2+, Ca 2+) which increase the potency of agonists for particulate receptors. The effects of Mg2+ can be reversed by Gpp(NH)p in particulate preparations; Gpp(NH)p is ineffective for the solubilized preparation. These experiments establish that beta-adrenergic receptors can be solubilized even from crude mammalian membrane preparations. They also show that the mammalian beta-adrenergic receptor in situ is under constraints with respect to agonist affinity and is modulated by divalent cations and guanyl nucleotides in the intact membrane.
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