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The FASEB Journal, Vol 5, 2300-2303, Copyright © 1991 by The Federation of American Societies for Experimental Biology

RESEARCH COMMUNICATIONS

Stoichiometry of receptor-Gs-adenylate cyclase interactions

AA Alousi, JR Jasper, PA Insel and HJ Motulsky
Department of Pharmacology, University of California, San Diego, La Jolla 92093.

Little is known about the relative stoichiometry of guanine nucleotide- binding (G) proteins relative to the effector systems to which they link. We addressed this question for the stimulatory G protein (Gs) linked to adenylate cyclase. Forskolin stimulates the catalytic subunit of adenylate cyclase (C), but it has a higher efficacy and potency when C also interacts with the G protein Gs. Accordingly, we measured high- affinity [3H]forskolin binding to intact cells to assay alpha s-C complexes. No high-affinity specific binding occurred with unstimulated cells. The beta-adrenergic agonist isoproterenol promoted the binding of [3H]forskolin to about 3000 sites per cell, suggesting that each receptor on average activates at least several Gs molecules. Activating Gs directly with cholera toxin maximally promoted [3H]forskolin binding to a similar number of sites, suggesting that this is the maximal number of alpha s-C complexes formed per cell. We conclude that each cell likely contains only a few thousand functional copies of C, and that the availability of C (rather than Gs, which exists in more than 100,000 copies per cell) is likely to be limiting for agonist stimulation of adenylate cyclase activity.


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Copyright © 1991 by The Federation of American Societies for Experimental Biology.