Regulation of coenzyme A biosynthesis by glucagon and glucocorticoid in adult rat liver parenchymal cells

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Abstract
The effects of glucagon [G], dibutyryl cyclic[c]AMP and dexamethasone [D] were studied on the rate of [14C]pantothenate conversion to CoA in adult rat liver parenchymal cells in primary culture. The presence of 30 nM-G increased the rate by .apprx. 1.5-fold relative to control cultures (range 1.4-2.3) and 2.4-fold relative to cultures containing 1-3 m-IU of insulin/ml. The half-maximal effect was obtained at 3 nM-G. Dibutyryl cAMP plus theophylline also enhanced the rate by .apprx. 1.5-fold. D acted synergistically with G; G at 0.3 nM had no effect when added alone, but resulted in a 1.7-fold enhancement when added in the presence of D (maximum effect at 50 mM). The 1.4-fold enhancement caused by the addition of saturating G concentrations was increased to a 3-fold overall enhancement by D addition. D added alone over the range 5 nM-5 .mu.M had no effect on the rate of [14C]pantothenate conversion to CoA. The stimulatory effect of dibutyryl cAMP plus theophylline was also enhanced by D addition. Changes in intracellular pantothenate concentration or radioactivity could not account for the stimulatory effects of G, dibutyryl cAMP or D. Addition of 18 .mu.M-cycloheximide, an inhibitor of protein synthesis, decreased the rate of incorporation of [14C]pantothenate into CoA and the enhancement of this rate by G and dibutyryl cAMP plus theophylline in a reversible manner. G, dibutyryl cAMP and glucocorticoids apparently influence the intracellular mechanism regulating total CoA concentrations in the liver.