Adenosine inhibits choline kinase activity and decreases the phosphorylation of choline in striatal synaptosomes.
The main objective of these studies was to determine whether adenosine inhibits choline kinase in rat striata, leading to a decreased incorporation of choline into phosphorylcholine, a mechanism that may mediate seizure-induced increases in the levels of free choline in brain. Incubation of particulate and soluble fractions of striatal synaptosomes with adenosine or its metabolically stable analogues significantly inhibited enzyme activity. The inhibition was noncompetitive versus choline and competitive versus MgATP. Inhibitor constants for adenosine, 2-chloroadenosine, and 2',5'-dideoxyadenosine at the MgATP site were 94, 49, and 207 microM, respectively; these values were less than the Michaelis constant for MgATP (340 microM). To determine whether adenosine altered the phosphorylation of choline in an intact preparation, synaptosomes were incubated with [3H]choline in the presence or absence of adenosine or its analogues and the amount of [3H]-phosphorylcholine formed from the [3H]choline taken up was measured. All compounds tested significantly reduced the synthesis of [3H]phosphorylcholine. Results suggest that following seizures or hypoxia, when levels of adenosine increase and the concentration of ATP decreases, inhibition of choline phosphorylation may be manifest, resulting in increased levels of free choline in brain.
Wecker
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Department of Pharmacology, Louisiana State University Medical Center, New Orleans 70112.
Reinhardt
R R
RR
D015762:2-Chloroadenosine; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002794:Choline / Q000378:metabolism*; D002797:Choline Kinase / Q000037:antagonists & inhibitors*; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology*; D003839:Deoxyadenosines / Q000031:analogs & derivatives / Q000494:pharmacology; D016048:Dideoxyadenosine / Q000031:analogs & derivatives*; D007700:Kinetics; D008297:Male; D010766:Phosphorylation; D010767:Phosphorylcholine / Q000378:metabolism; D010770:Phosphotransferases / Q000037:antagonists & inhibitors*; D051381:Rats; D011919:Rats, Inbred Strains; D013574:Synaptosomes / Q000201:enzymology*
D003839:Deoxyadenosines; D010767:Phosphorylcholine; D015762:2-Chloroadenosine; D016048:Dideoxyadenosine; D000255:Adenosine Triphosphate; C021008:2',5'-dideoxyadenosine; D010770:Phosphotransferases; D002797:Choline Kinase; D000241:Adenosine; D002794:Choline