Cholesterol modulation of β-adrenergic receptor characteristics |
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Authors: | Philip J Scarpace Stephen W OConnor Itamar B Abrass |
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Institution: | 1. Geriatric Research, Education and Clinical Center (GRECC), Sepulveda VA Medical Center, Sepulveda, CA 91343, U.S.A.;2. Department of Medicine, UCLA School of Medicine, Los Angeles, CA 90024 U.S.A. |
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Abstract: | Cholesterol, a major structural component of plasma membranes, has a profound influence on cell surface receptor characteristics and on adenylate cyclase activity. β-Adrenergic receptor number, adenylate cyclase activity, and receptor-cyclase coupling were assessed in rat lung membranes following preincubation with cholesteryl hemisuccinate. β-Adrenergic receptor number increased by 50% without a change in antagonist affinity. However, β-adrenergic receptor affinity for isoproterenol increased 2-fold as a result of an increase in the affinity of the isoproterenol high-affinity binding site. This increase in agonist affinity did not potentiate hormone-stimulated adenylate cyclase activity, which decreased 3-fold following cholesterol incorporation. However, the ratio of isoproterenol to GTP-stimulated activity was unchanged with cholesterol. Stimulation distal to the receptor by GTP, NaF, GppNHp, Mn2+ and forskolin also demonstrated 50–80% reduced enzyme activity following cholesterol incorporation. These data suggest that membrane cholesterol incorporation decreases catalytic unit activity without affecting transduction of the hormone signal. |
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Keywords: | Cholesterol modulation β-Adrenergic receptor Hepes 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid |
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