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Decreased Cyclic AMP Degradation in NG 108‐15 Neuroblastoma × Glioma Hybrid Cells and S49 Lymphoma Cells Chronically Treated with Drugs that Inhibit Adenylate Cyclase
Author(s) -
Thomas John M.,
Vagelos Randall,
Hoffman Brian B.
Publication year - 1990
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1990.tb01887.x
Subject(s) - adenylate kinase , cyclase , neuroblastoma , lymphoma , chemistry , cancer research , glioma , medicine , endocrinology , biology , cell culture , biochemistry , enzyme , genetics
The increase in hormone‐stimulated cyclic AMP accumulation observed in a variety of intact cells after chronic pretreatment with drugs that inhibit adenylate cyclase activity has been attributed to an increase in adenylate cyclase activity following withdrawal of the inhibitory drug. In NG 108–15 mouse neuroblastoma X rat glioma hybrid cells (NG cells) chronically treated with the muscarinic cholinergic agonist carbachol, we have found a significant decrease in the apparent degradation rate constant for cyclic AMP, in addition to an increase in the prostaglandin E 1 (PGE 1 )‐stimulated cyclic AMP synthesis rate in intact cells. In carbachol‐pretreated NG cells that were stimulated with a maximally effective dose of PGE 1 , and that accumulated steady‐state cyclic AMP concentrations fourfold or more higher than in control cells, the apparent rate constant for degradation was about 53% lower than the value for control cells. In carbachol‐pretreated cells stimulated with a submaximal dose of PGE 1 to yield a steady‐state cyclic AMP concentration comparable to control cells, the apparent rate constant was 31% lower than the value for control cells. In S49 mouse lymphoma cells (S49 cells) chronically treated with an analog of the inhibitory agonist somatostatin, the first‐order rate constant for cyclic AMP degradation in intact cells following isoproterenol stimulation was 29% lower than the value for control cells. Despite these changes in the kinetics of cyclic AMP degradation in intact NG cells and S49 cells, there was either no change or a minimal change (less than 10%) in phosphodiesterase activities assayed in extracts of cells chronically exposed to inhibitory drugs. These data suggest that an alteration in cyclic AMP degradation as well as in cyclic AMP synthesis is an important factor in the withdrawal response following chronic treatment of cells with drugs that inhibit adenylate cyclase.