Guanosine 3',5'-monophosphate and the action of alkylating agents.
The intracellular level of guanosine 3',5'-monophosphate (cGMP) has been measured in Walker carcinoma cells in tissue culture after treatment with various alkylating agents. At concentrations which caused a rise in the level of adenosine 3',5'-monophosphate (cAMP) chlorambucil and 5-(1-aziridinyl)-2,4-dinitrobenzamide (CB 1954) produced only a small (35%) elevation of cGMP, while merophan had no such effect. This suggests that any effect of cAMP will not be outweighed by an equivalent rise in cGMP. Sepcific cytosolic binding of cGMP decreased with increasing resistance of Walker cells to alkylating agents, while the dissociation constant, KD, for binding increased. This was also observed with cAMP binding which suggests that the same protein in responsible for binding both nucleotides.
D000477:Alkylating Agents / Q000494:pharmacology*; D000818:Animals; D001388:Aziridines / Q000494:pharmacology*; D001389:Azirines / Q000494:pharmacology*; D002279:Carcinoma 256, Walker; D002478:Cells, Cultured; D002699:Chlorambucil / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D004351:Drug Resistance; D007700:Kinetics; D009363:Neoplasm Proteins / Q000378:metabolism; D011485:Protein Binding
D000477:Alkylating Agents; D001388:Aziridines; D001389:Azirines; D009363:Neoplasm Proteins; D002699:Chlorambucil; D000242:Cyclic AMP; D006152:Cyclic GMP