Desensitization of mammalian. beta. -adrenergic receptors: receptor sequestration vs. receptor function
Human A431 and rat glioma C6 cells exposed to isoproterenol (ISO) underwent a time and dose dependent loss of ISO-stimulated adenylate cyclase (AC) activity (desensitization). In addition, ..beta..-adrenergic receptors (..beta..AR) became less accessible to the hydrophilic antagonist (/sup 3/H)CGP-12177 and redistributed from the heavier density plasma membrane fraction to a lighter density membrane fraction (sequestration). Pretreatment of the cells with Concanavalin A (Con A) or phenylarsine oxide blocked sequestration but not desensitization. ..beta..AR of membranes prepared from Con A-pretreated cells exhibited a reduced affinity for ISO after desensitization as measured by the half-maximal concentration of ISO required to stimulate AC (Kact) and to compete for antagonist binding (IC50). Membranes were exposed to alkali to inactivate AC and ..beta..AR was transferred to a foreign AC by membrane fusion with polyethylene glycol. ..beta..AR from desensitized cells exhibited a reduced affinity for ISO (both Kact and IC50) and a reduced ability to stimulate the foreign AC. In addition, ..beta..AR from desensitized cells remained accessible to (/sup 3/H)CGP-12177 in the fused membranes. The authors conclude that the primary, essential step in desensitization is a reduction in ..beta..AR function. In contrast, ..beta..AR sequestration is not a prerequisite but a secondary event in the desensitization process.
- Research Organization:
- National Institutes of Health, Bethesda, MD
- OSTI ID:
- 5220263
- Report Number(s):
- CONF-8606151-
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:6; Conference: 76. annual meeting of the Federation of American Society for Experimental Biology, Washington, DC, USA, 8 Jun 1986
- Country of Publication:
- United States
- Language:
- English
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550201* - Biochemistry- Tracer Techniques