Insulin activation of cyclic AMP phosphodiesterase in intact ureteral segments

RM Weiss and MA Wheeler

Yale University School of Medicine, Department of Surgery/Urology, New Haven, Connecticut.

Low doses of insulin (0.1-50 nM) when presented to intact ureteral segments increase cyclic AMP (cAMP) phosphodiesterase (PDE) activity in subsequently isolated supernatant and particulate fractions. The stimulation of cAMP PDE occurs within 5 to 10 min of the introduction of insulin. When cyclic GMP or high concentrations of cAMP (greater than 5 microM) are used as substrate, insulin does not increase PDE activity. Although the insulin-increased cAMP PDE exhibits the same sensitivity as control PDE from untreated preparations to isobutylmethyl xanthine, a nonspecific PDE inhibitor, and M & B 22,948, a relatively selective cyclic GMP PDE inhibitor, differences in the degree of inhibition of PDE activity are seen in the insulin-treated and untreated preparations with the low Km cAMP PDE inhibitors Ro20- 1724, rolipram, amrinone and milrinone and with cyclic GMP. Pertussis toxin, which modifies GTP regulatory proteins of the adenylate cyclase enzyme and the photoreceptor PDE, blocks cAMP PDE activation by insulin.

Volume 247, Issue 2, pp. 630-634, 11/01/1988
Copyright © 1988 by American Society for Pharmacology and Experimental Therapeutics