Differential inhibition of phosphodiesterase according to the organ origin of the enzyme

Abstract

Essential differences in the degree of papaverine [5 x 10(-5) M]- and theophylline [1 x 10(-3) M]-induced inhibition of cyclic nucleotide phosphodiesterase (PDE) were found in homogenates from different structures of the CNS as well as from different organs of male albino rats. Both inhibitors of PDE showed a mosaic pattern of their inhibitory effects on the enzyme activity of the brain structures tested. Papaverine inhibited PDE by 36 percent in the spinal cord, 53 percent in the cerebellum, 56 percent in the cortex, and 75 percent in the brain stem. Theophylline inhibited PDE least in the cerebellum (26 percent ) and most markedly in the brain stem (68 percent). Still larger differences were observed in the inhibitory action of papaverine and theophylline on PDE of the organs tested (e.g., papaverine inhibited PDE by 6 percent in the heart and 73 percent in the spleen; theophylline inhibited PDE by 26 percent in the adrenals and by 72 percent in the heart. The mosaic sensitivity of PDE in different organs and brain structures to papaverine and theophylline was considered as an expression of isoenzyme heterogeneity.