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Vol. 290, Issue 3, 980-988, September 1999

Coupling Efficiencies of beta 1- and beta 2-Adrenergic Receptors Expressed Alone or Together in Transfected GH3 Pituitary Cells1

Shelly Wood Guerrero and Kenneth P. Minneman

Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia

The relationship between rat beta 1- and beta 2-adrenergic receptors (ARs) and cyclic AMP (cAMP) responses was examined by inducible expression of each subtype in transfected GH3 pituitary cells. Increasing expression of beta 1- or beta 2-ARs in stably transfected subclones increased basal cAMP, increased the potency of isoproterenol in stimulating cAMP formation, but did not change the maximal response. A linear relationship was observed between log Bmax and -log EC50 for isoproterenol, with no significant differences between beta 1- and beta 2-ARs. When both subtypes were coexpressed at different densities and ratios, pharmacological analysis showed that both selective and nonselective agonists exerted their effects at least partially through both subtypes. Either subtype alone activated a maximal response when the other subtype was blocked, indicating a complete redundancy in coupling. Agonists could activate responses through either subtype, with responses mediated primarily through the subtype where the agonist was most potent. The nonselective agonist isoproterenol had similar potencies for activating both subtypes; however, the density and ratio of subtypes affected the relative potencies of the selective agonists norepinephrine and zinterol. We conclude that beta 1- and beta 2-ARs have similar coupling efficiencies in GH3 cells, these efficiencies are not altered by coexpression of another subtype, they couple redundantly to cAMP formation, and the relative densities of beta 1- and beta 2-ARs control the potencies of selective agonists.

0022-3565/99/2903-0980$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 1999 by The American Society for Pharmacology and Experimental Therapeutics


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