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Guanine nucleotide regulation of. cap alpha. /sub 1/-adrenergic receptors of muscle and kidney eptihelial cells

Conference · · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)
OSTI ID:5151403
; ; ;

The authors have examined the effect of guanine nucleotides on the interaction of adrenergic agents with ..cap alpha../sup 1/-adrenergic receptors of two cell lines, the Madin-Darby Canine Kidney (MDCK) and BC3H-1 muscle cells. While gaunylylimidodiphosphoate (Gpp(NH)p) had no effect on the affinity or the total number of (/sup -3/H)prazosin binding sites in membranes prepared from these cells, the nucleotide decreased the apparent affinity of the agonist epinephrine in competing for (/sup 3/H)prazosin binding sites in both cell types. The EC/sub 50/ of Gpp(NH)p was approx.100 ..mu..M, and a maximal effect was seen at 500 ..mu..M. In contrast, 100 ..mu..M Gpp(NH)p yielding maximal shifts in binding of epinephrine to ..beta..-adrenergic receptors in BC3H-1 cell membranes. Guanine nucleotides were significantly more effective than adenine nucleotides in shifting agonist affinity for the ..cap alpha../sub 1/-receptor and Mg/sup + +/ was required to observe a maximal effect. ..cap alpha../sub 1/-receptor agonists activated phosphatidylinositol (PI) hydrolysis in both cell types, but have no direct effect on membrane adenylate cyclase activity. In intact BC3H-1 cells, ..cap alpha../sub 1/-agonists inhibited ..beta..-adrenergic cAMP production, an effect which appears in preliminary studies not to result from enhanced phosphodieterase activity. These results show that agonist binding to ..cap alpha../sup 1/-adrenergic receptors in mammalian kidney and muscle cells is regulated by guanine nucleotides. This regulation and inturn transmembrane signalling (PI hydrolysis) by these receptors appear to involve a guanine nucleotide binding (G) protein, which may be different than G/sub s/ and G/sub i/.

Research Organization:
Univ. of California San Diego, La Jolla
OSTI ID:
5151403
Report Number(s):
CONF-8606151-
Journal Information:
Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Vol. 45:6; ISSN FEPRA
Country of Publication:
United States
Language:
English

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Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ADENINES
ADRENAL HORMONES
ADRENALINE
AFFINITY
AMINES
ANIMAL TISSUES
ANTIMETABOLITES
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZAARENES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
BODY
CARDIOTONICS
CARDIOVASCULAR AGENTS
CELL CONSTITUENTS
CELL CULTURES
CELL MEMBRANES
CHEMICAL REACTIONS
CYCLASES
DECOMPOSITION
DRUGS
ENZYME ACTIVITY
ENZYMES
EPITHELIUM
ESTERS
GUANINE
HETEROCYCLIC COMPOUNDS
HORMONES
HYDROLYSIS
HYDROXY COMPOUNDS
KIDNEYS
KINETICS
LABELLED COMPOUNDS
LIPIDS
LYASES
LYSIS
MEMBRANE PROTEINS
MEMBRANES
MUSCLES
NEUROREGULATORS
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
ORGANS
PHOSPHOLIPIDS
PROTEINS
PURINES
REACTION KINETICS
RECEPTORS
SOLVOLYSIS
STEROID HORMONES
SYMPATHOMIMETICS
TISSUES
TRITIUM COMPOUNDS