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Endogenous ADP-ribosylation of Gs subunit and autonomous regulation of adenylate cyclase

Abstract

Although cholera toxin induces a marked stimulation of adenylate cyclase activity in rat adipocyte plasma membranes1, the holotoxin induces only a slight increase of cyclic AMP accumulation in intact cells2. A similar apparent anomaly is seen with pertussis toxin, which has been shown to inhibit the Gi subunit of adenylate cyclase, and has a greater effect on cAMP accumulation and lipolysis than the activation by cholera toxin of the Gs subunit3. To understand better the way in which these bacterial toxins are modifying the adipocyte cells, we prepared adipocyte plasma membranes and submitted them to ADP-ribosylation by cholera and pertussis toxins. During the incubation of control cells, we found endogenous ADP-ribosylation of Gs as a result of sustained stimulation of Gi by adenosine. Our results point to a possible homoeos-tatic system in which the autonomous adjustment of the basal activity of Gs as a function of that of Gi, under the control of feedback inhibitory ligands, ensures a steady production of cAMP within the cell.

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Jacquemin, C., Thibout, H., Lambert, B. et al. Endogenous ADP-ribosylation of Gs subunit and autonomous regulation of adenylate cyclase. Nature 323, 182–184 (1986). https://doi.org/10.1038/323182a0

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