Phosphodiesterase activity of the lower urinary tract

Cyclic AMP is believed to mediate the physiologic response of beta-receptor stimulation in the lower urinary tract. A possible novel therapy for specific dysfunctions might be via pharmacologic modification of cyclic AMP through regulation of phosphodiesterase, the enzyme responsible for metabolizing cyclic AMP. The present study characterizes the phosphodiesterase activity present in various sections of the lower urinary tract and determines the effect of calmodulin and the potency of a series of phosphodiesterase inhibitors. The results can be summarized as follows: the phosphodiesterase activity of all smooth muscle sections of the lower urinary tract were similar. They showed nonlinear kinetics with Vmax between 1.0 and 2.4 nmol./mg. protein/minute and apparent Km's around 100 microM. The external sphincter (skeletal muscle) displayed linear kinetics with a Vmax of 0.2 nmol./mg. protein/minute and a Km of 9 microM. Of the drugs tested, papaverine was the most potent inhibitor and theophylline was one of the weakest inhibitors. These studies also indicate that the major form of cyclic AMP phosphodiesterase is not sensitive to calmodulin.