INDUCTION OF REFRACTORINESS TO ISOPROTERENOL BY PRIOR TREATMENT OF C6-2B RAT ASTROCYTOMA-CELLS WITH CHOLERA-TOXIN

  • 1 January 1979
    • journal article
    • research article
    • Vol. 5  (6) , 435-447
Abstract
Rat C6-2B astrocytoma cells responded to cholera toxin treatment with an 8-fold increase in intracellular cyclic[c]AMP concentrations. cAMP levels began to rise 60-90 min after addition of the toxin and reached maximal concentrations in 3 h. Cells exposed to cholera toxin and the phosphodiesterase inhibitor, 1-methyl-3-isobutylxanthine (MIX), displayed an increase in cAMP of 15-fold. The peak isoproterenol response was reduced 80-90% in cells previously treated with cholera toxin. Cholera toxin-induced refractoriness was time dependent and was not altered by concurrent treatment with propranolol. Prolonged exposure of the cells to isoproterenol reduced the cAMP response to cholera toxin by 80%. MIX augmented cholera toxin-induced refractoriness and isoproterenol-induced refractoriness. Cycloheximide inhibited the full development of refractoriness to cholera toxin and isoproterenol. C6-2B cell refractoriness to cholera toxin may be mediated by cAMP and requires new protein synthesis. Refractoriness in C6-2B cells may not be agonist-specific and probably involves a common locus of action on adenylate cyclase beyond that of the membrane receptors for cholera toxin and isoproterenol.

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