Increase in hormonal activation of adenylate cyclase by treatment of cultured cells with N-alkyl,N-nitrosourea.
Treatment of cultured normal rat kidney cells with the nitrosourea-containing compounds streptozotocin, chlorozotocin, or 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea resulted in a time-dependent potentiation in the ability of prostaglandin E1 and (-)-isoproterenol to elevate intracellular cAMP levels. This hormone response increased at 4 hours and reached a maximum at 15--25 hours after addition of the nitrosoureas. Basal cAMP levels were not affected. The greater response was apparently due to an increase in the GTP-dependent step in hormonal activation of adenylate cyclase, inasmuch as GTP- and GTP plus hormone-stimulated adenylate cyclase activities were enhanced twofold to threefold in crude membranes prepared from nitrosourea-treated cells. Fluoride-stimulated adenylate cyclase activity was increased only 10--25%. Nicotinamide did not prevent the elevated response, and NAD+ plus NADH levels were not appreciably altered after 42 hours; treatment with streptozotocin. The results suggest a possible involvement of cAMP in the biologic actions of nitrosoureas.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology*; D007668:Kidney; D009243:NAD / Q000378:metabolism; D009607:Nitrosourea Compounds / Q000494:pharmacology*; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology*; D051381:Rats; D013311:Streptozocin / Q000494:pharmacology
D009607:Nitrosourea Compounds; D011459:Prostaglandins E, Synthetic; D009243:NAD; D013311:Streptozocin; D000262:Adenylyl Cyclases; D007545:Isoproterenol