Desensitization of mammalian. beta. -adrenergic receptors: receptor sequestration vs. receptor function

Conference · Thu May 01 04:00:00 EDT 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:5220263

Kassis, S; Olasmaa, M; Fishman, P H

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-
• Conference Information: Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 45:6
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AFFINITY
AGGLUTININS
ANIMALS
ANTIBODIES
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL FUNCTIONS
BIOLOGICAL MATERIALS
BLOOD
BLOOD PLASMA
BODY FLUIDS
CELL CONSTITUENTS
CELL MEMBRANES
CONCANAVALIN
CYCLASES
DISEASES
DOSE-RESPONSE RELATIONSHIPS
DRUGS
ENZYME ACTIVITY
ENZYMES
FUNCTIONS
GLIOMAS
HEMAGGLUTININS
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
LECTINS
LYASES
MAMMALS
MAN
MATERIALS
MEMBRANE PROTEINS
MEMBRANES
NEOPLASMS
ORGANIC COMPOUNDS
PRIMATES
PROTEINS
RATS
REACTION KINETICS
RECEPTORS
RODENTS
SYMPATHOMIMETICS
TIME DEPENDENCE
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES