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Molecular Pharmacology

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Abstract

Differential expression of the beta-adrenergic receptor modifies agonist stimulation of adenylyl cyclase: a quantitative evaluation.

B S Whaley, N Yuan, L Birnbaumer, R B Clark and R Barber
Molecular Pharmacology March 1994, 45 (3) 481-489;
B S Whaley
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N Yuan
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L Birnbaumer
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R B Clark
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R Barber
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Abstract

The effect of varying levels of beta 2-adrenergic receptor (beta AR) expression on the capacity of the receptor to activate adenylyl cyclase through regulatory G proteins has been systematically explored in this paper, using differential expression of hamster and human beta AR in L cells. Equations have been developed based on the cycle of G protein activation first proposed by Cassel and Selinger and the mobile receptor model, which assumes that hormone-bound beta AR can stimulate a number of different adenylyl cyclase moieties through the G protein during a single cycle of activation. These equations predict the relationship of receptor number to the EC50 (potency) and Vmax (efficacy) for adenylyl cyclase activation. L cell clones were selected with stable expression of the beta AR over a 2000-fold range of levels (from 5 to 10,000 fmol/mg of membrane protein). Experimentally determined values for the EC50 and the Vmax for epinephrine stimulation of adenylyl cyclase over the entire range of receptor levels were found to be in excellent agreement with predictions of the traditionally accepted models. A method is introduced that allows calculation of beta AR coupling efficiency while taking into account the effect of variable receptor levels. The approach provides a quantitative means for the determination of coupling efficiency of the receptor/G protein/adenylyl cyclase system over wide variations in receptor levels and allows for a rational comparison of coupling efficiencies of wild-type and mutant receptors when receptor levels differ.

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Molecular Pharmacology
Vol. 45, Issue 3
1 Mar 1994
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Abstract

Differential expression of the beta-adrenergic receptor modifies agonist stimulation of adenylyl cyclase: a quantitative evaluation.

B S Whaley, N Yuan, L Birnbaumer, R B Clark and R Barber
Molecular Pharmacology March 1, 1994, 45 (3) 481-489;

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Abstract

Differential expression of the beta-adrenergic receptor modifies agonist stimulation of adenylyl cyclase: a quantitative evaluation.

B S Whaley, N Yuan, L Birnbaumer, R B Clark and R Barber
Molecular Pharmacology March 1, 1994, 45 (3) 481-489;
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