Guanine nucleotide regulation of. cap alpha. /sub 1/-adrenergic receptors of muscle and kidney eptihelial cells
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), 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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ADRENALINE
BIOCHEMICAL REACTION KINETICS
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ADENINES
AFFINITY
CELL CULTURES
CELL MEMBRANES
CYCLASES
ENZYME ACTIVITY
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CARDIOVASCULAR AGENTS
CELL CONSTITUENTS
CHEMICAL REACTIONS
DECOMPOSITION
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HORMONES
HYDROXY COMPOUNDS
KINETICS
LABELLED COMPOUNDS
LIPIDS
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ORGANIC COMPOUNDS
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SOLVOLYSIS
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550201* - Biochemistry- Tracer Techniques