Effects of two nucleoside transport inhibitors, dipyridamole and soluflazine, on purine release from the rat cerebral cortex.
The effects of two nucleoside transport inhibitors, dipyridamole and soluflazine, on adenosine, inosine and oxypurine release from the normoxic and hypoxic/ischemic rat cerebral cortex have been studied. Dipyridamole (500 micrograms/kg) enhanced adenosine release during hypoxic/ischemic challenges in comparison with saline-injected controls. It decreased the hypoxia/ischemia-elicited releases of inosine, hypoxanthine and xanthine. Both basal and hypoxia/ischemia-elicited releases of uric acid were elevated. Soluflazine, administered topically or systemically, failed to enhance adenosine release and did not consistently alter the hypoxia/ischemia-evoked releases of inosine, hypoxanthine and xanthine. Basal release of uric acid was elevated. The failure of either drug to elevate the basal or hypoxia/ischemia-evoked releases of adenosine above predrug levels illustrates one of the problems which may be inherent in the use of bidirectional nucleoside transport inhibitors for the manipulation of adenosine levels in the cerebral interstitial fluid.
Phillis
J W
JW
Department of Physiology, School of Medicine, Wayne State University, Detroit, MI 48201.
O'Regan
M H
MH
Walter
G A
GA
D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002545:Brain Ischemia / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D004176:Dipyridamole / Q000494:pharmacology*; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D011687:Purines / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D010879:Piperazines; D011687:Purines; C054695:soluflazine; D004176:Dipyridamole; D000241:Adenosine