Cholera toxin blocks glucagon-mediated inhibition of the liver plasma membrane (Ca2+-Mg2+)-ATPase.

S Lotersztajn,C Pavoine,A Mallat,D Stengel,P.A Insel,F Pecker

doi:10.1016/s0021-9258(18)61476-0

Abstract

We have previously shown that liver plasma membrane (Ca2+-Mg2+)-ATPase activity is inhibited by glucagon. To investigate the possible involvement of a GTP-binding (G) protein in this regulation, we have examined the effects of pertussis toxin and cholera toxin on inhibition of (Ca2+-Mg2+)-ATPase by glucagon. Treatment of liver plasma membranes with pertussis toxin did not affect the sensitivity of (Ca2+-Mg2+)-ATPase to the hormone. In contrast, treatment of plasma membranes or prior injection of animals with cholera toxin prevented inhibition of the (Ca2+-Mg2+)-ATPase by glucagon. Even though adenylate cyclase activity was increased by cholera toxin treatment, addition of cyclic AMP did not mimic the effect of cholera toxin in blocking glucagon-mediated inhibition of (Ca2+-Mg2+)-ATPase activity. These data suggest that a cholera toxin-sensitive protein, perhaps Gs or a Gs-like protein, is involved in the regulation of liver (Ca2+-Mg2+)-ATPase activity. The results emphasize the possible role of Gs-like proteins in regulation of enzymes other than adenylate cyclase and suggest that the study of (Ca2+-Mg2+)-ATPase may provide a useful enzymatic system to examine such regulation.

Highlights

We have previously shown that liver plasma mem- only in the presence of the activator andM e (6)
I n a first series of experiments, we studied the responseof or its inhibitor (30,000 Da, Refs. 6 a n d 7) respectively, was the (Ca*+-M$+)-ATPase to glucagon after treatment of the detected (Fig. 2C). liver plasma membranes with cholera toxin
In cholera toxin-treated membranes addition of 4 WM glucagon to control membranes resulted in no inhibition by glucagon was observe(dFig. 1A). It is known a 18 f 3% inhibition of (Ca'+-M$+)-ATPase activity, halfthat choleratoxintreatment,whichinhibits the GTPase maximal inhibition being observed with 2 FM glucagon.In activity of t h e cy subunit of G, leads toa persistent activation plasma membranes obtained from cholera toxin-treated rats, of adenylate cyclase activity(26-28)

Summary

Introduction

We have previously shown that liver plasma mem- only in the presence of the activator andM e (6). Treatment of plasma membranes or prior injection of animals with cholera toxin prevented inhibition of the (Ca2+-Mg2+)ATPase by glucagon.

Results

Conclusion