Abstract
The antilipolytic potencies of insulin and several heterocyclic carboxylic acids (nicotinic acid, 3-methylisoxazole-5-carboxylic acid, 3-methyl pyrazole-5-carboxylic acid) revealed marked differ ences after stimulation of lipolysis in isolated fat cells by lipolytic hormones and theophylline. Insulin pro duced strong inhibition of noradrenaline- and ACTH-induced lipolysis but only partly antagonized the lipolytic effect of theophylline. On the other hand, nicotinic acid, 3-methylisoxazole-5-carboxylic acid and 3-methyl-ρyrazole-5-carboxylic acid had only weak effects on the hormonal stimulation of lipolysis but proved to be potent inhibitors of theophylline-induced lipolysis. High concentrations of theophylline were able to overcome the inhibitory effect of the carboxylic acids indicating a competitive type of antagonism. Lipolysis induced by dibutyryl cyclic AMP was not influenced by any of the four antilipolytic agents studied. Neither insulin nor the heterocyclic carboxylic acids affected the activity of cyclic AMP phosphodiesterase of adipose tissue homogenates even in micromolar concentrations of cyclic AMP. These results suggest that the heterocyclic carboxylic acids antagonize the lipolytic effect of theophylline at a site different from phosphodiesterase.
Published Version
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