Endogenous cyclic AMP does not modulate transport of hexoses, nucleosides, or nucleobases in Chinese hamster ovary cells.
In a previous study we have demonstrated that neither extracellular nor intracellular cyclic adenosine monophosphate (AMP) levels directly affect the uptake of nucleosides, nucleobases, or hexoses by various types of cultured mammalian cells. Uptake of these nutrients into cells, however, involves two processes operating in tandem: facilitated transport across the membrane and intracellular phosphorylation; and uptake rates generally reflect the rates of substrate phosphorylation rather than of transport. In the present study we have examined the question of whether substrate transport per se is regulated by intracellular cyclic AMP. Initially various cell lines, grown both in suspension and monolayer culture, were screened for their cyclic AMP response to prostaglandin E1, isoproterenol, and inhibitors of cyclic AMP phosphodiesterase. Prostaglandin E1 treatment of Chinese hamster ovary cells was selected as the system giving the largest and most consistent (50-fold to 100-fold) elevation of cyclic AMP. Rapid kinetic techniques were used to measure the transport of 3-O-methylglucose, thymidine, adenosine, hypoxanthine, and adenine in wild-type cells and in mutant sublines incapable of phosphorylating these substrates. In no case was an increase in intracellular cyclic AMP accompanied by a significant change in the rate of transport of these substrates, although prostaglandin E1 slightly inhibited the transport of various substrates.
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism*; D005260:Female; D006601:Hexoses / Q000378:metabolism; D009154:Mutation; D009705:Nucleosides / Q000378:metabolism*; D010053:Ovary / Q000378:metabolism*; D011458:Prostaglandins E / Q000494:pharmacology; D011687:Purines / Q000378:metabolism*; D011743:Pyrimidines / Q000378:metabolism*
D006601:Hexoses; D009705:Nucleosides; D011458:Prostaglandins E; D011687:Purines; D011743:Pyrimidines; D000242:Cyclic AMP