The Effect of in Vitro and in Vivo Caffeine,Theophylline,and Hydrocortisone on the Phosphodiesterase Activity of the Pituitary,Median Eminence,Heart,and Cerebral Cortex of the Rat

Abstract

Summary

This study was undertaken to substantiate the thesis that the potentiation of the stress-induced secretion of ACTH by the methyl xanthines is due to their ability to inhibit the 3′5′-cyclic nucleotide phosphodiesterase. The effect of various drugs on the phosphodiesterase activity of the anterior pituitary, median eminence, brain cortex, and heart of rats was determined both in vitro and in vivo. Incubation of homogenates with caffeine and theophylline markedly reduced the phosphodiesterase activity in all tissues studied except heart, which showed a significant reduction only in the presence of theophylline. In contrast, pretreating the animals with a single dose of caffeine or theophylline reduced the enzyme activity of the anterior pituitary only, and caffeine was more effective than theophylline. Adrenalectomy, chronic or acute administration of hydrocortisone, or incubation of tissue homogenates with hydrocortisone or dexamethasone did not alter the phosphodiesterase activity of the tissues studied. It is concluded that the effects of caffeine and theophylline on the pituitary stress response could be attributed to their inhibition of the phosphodiesterase activity in that tissue.