Reversal of Catecholamine Refractoriness by Inhibitors of RNA and Protein Synthesis

The generation of adenosine 3',5'-monophosphate (cyclic AMP) in response to catecholamines in the 2B subclone of RGC6 rat glioma cells previously exposed to norepinephrine and refractory to further norepinephrine addition is substantially increased by addition of inhibitors of RNA and protein synthesis. The time course of the effect of these inhibitors on cyclic AMP concentration suggests that rapid protein synthesis and turnover are involved in catecholamine refractoriness. Norepinephrine induction of cyclic nucleotide phosphodiesterase is demonstrable in RGC6 cells but not in the 2B subclone. Thus, catecholamine refractoriness cannot be attributed to induction of phosphodiesterase. This implies that induction of a protein or proteins, important in catecholamine refractoriness, affects the synthesis rather than the degradation of cyclic AMP.