Cyclic AMP levels of C6 glioma cells treated with cis-dichlorodiammine platinum (cis-DDP).
Rat C6 glioma cells were cultured for 3-4 days in MEM supplemented with bovine serum. After 10 min incubation of cells with 0.075, 1.0 or 7.5 micrograms ml-1 cis-DDP the basal cAMP levels (7.87 +/- 0.4 pmoles mg-1 protein) were not affected. In the presence of a phosphodiesterase inhibitor, IBMX, an increase of cAMP occurred; the later was more pronounced in cis-DDP treated cells than in the controls. This suggests that both adenylate cyclase and cAMP-phosphodiesterase were proportionally influenced at this period and that the stimulatory effect of cis-DDP on AC could be demonstrated only when increased activity of PDE had been blocked by IBMX. At later time intervals (10 h-40 h), a 5- to 17-fold elevation of cAMP levels was observed even in the absence of IBMX. Pretreatment of the cells with cis-DDP significantly potentiated cAMP accumulation in response to NE alone and to cis-DDP plus NE could be prevented to a large extent by propranolol; in cis-DDP treated cells the propranolol protection was more effective, both in the absence and the presence of IBMX. The pretreatment of cells with an alpha-blocker, Regitin, did not significantly influence cAMP accumulation. The results indicate that the cis-DDP stimulated cAMP response to NE is mediated via an interaction with beta-adrenergic receptors. The late increase in cAMP content may be a mediator of the morphological changes in these cells following exposure to cis-DDP.
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D002945:Cisplatin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism*; D005910:Glioma / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats
D011433:Propranolol; D000242:Cyclic AMP; D002945:Cisplatin; D009638:Norepinephrine