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Abstract

Coexisting beta-1 and beta-2-adrenergic receptors with differential receptor reserves in rat C6 glioma cells.

H Zhong and K P Minneman
Journal of Pharmacology and Experimental Therapeutics March 1995, 272 (3) 1088-1094;
H Zhong
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Abstract

The coupling efficiencies of beta-1 and beta-2-adrenergic receptors (ARs) in rat C6 glioma cells and the effect of changes in subtype density and ratio caused by dexamethasone (DEX) treatment were studied. Radioligand binding studies in membranes suggested that beta-2-ARs showed slightly larger GTP-induced decreases in agonist affinity than beta-1-ARs, which suggests more ternary complex formation with Gs. Treatment with DEX increased the proportion of beta-2-ARs from 20% to 60% without affecting GTP-induced decreases in agonist affinity. Coupling efficiency was determined directly by progressive inactivation of beta-ARs with the irreversible alkylating agent pindobind, which caused similar reductions in beta-1 and beta-2-AR binding sites. Studies on cyclic AMP accumulation showed that DEX-induced decreases in beta-1/beta-2 ratio reduced the receptor reserve for the beta-1-selective agonist norepinephrine but increased the maximal response to the beta-2-selective agonist zinterol without creating a receptor reserve. DEX treatment did not alter occupancy-response curves or maximal responses to the nonselective agonists isoproterenol and epinephrine. It was concluded that changing beta-2-AR density alters the maximal response to beta-2-AR activation; changing beta-1-AR density alters the apparent beta-1-AR reserve. Both subtypes contribute to the responses to nonselective agonists in a nonadditive manner. Beta-1- and beta-2-ARs appear to couple with different efficiencies (beta-1 > beta-2) to cyclic AMP accumulation in C6 glioma cells.(ABSTRACT TRUNCATED AT 250 WORDS)

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Journal of Pharmacology and Experimental Therapeutics
Vol. 272, Issue 3
1 Mar 1995
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Abstract

Coexisting beta-1 and beta-2-adrenergic receptors with differential receptor reserves in rat C6 glioma cells.

H Zhong and K P Minneman
Journal of Pharmacology and Experimental Therapeutics March 1, 1995, 272 (3) 1088-1094;

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Abstract

Coexisting beta-1 and beta-2-adrenergic receptors with differential receptor reserves in rat C6 glioma cells.

H Zhong and K P Minneman
Journal of Pharmacology and Experimental Therapeutics March 1, 1995, 272 (3) 1088-1094;
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