Insulin activation of cyclic AMP phosphodiesterase in intact ureteral segments.
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.
Weiss
R M
RM
Yale University School of Medicine, Department of Surgery/Urology, New Haven, Connecticut.
Wheeler
M A
MA
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism*; D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / Q000494:pharmacology; D000676:Amrinone / Q000494:pharmacology; D000818:Animals; D006152:Cyclic GMP / Q000494:pharmacology; D004789:Enzyme Activation; D005260:Female; D006168:Guinea Pigs; D007328:Insulin / Q000494:pharmacology*; D007700:Kinetics; D020105:Milrinone; D011688:Purinones / Q000494:pharmacology; D011728:Pyridones / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D020889:Rolipram; D014513:Ureter / Q000201:enzymology*
D007328:Insulin; D011688:Purinones; D011728:Pyridones; D011760:Pyrrolidinones; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; C011145:zaprinast; D006152:Cyclic GMP; D020105:Milrinone; D000676:Amrinone; D020889:Rolipram