Involvement of P2 purinoceptors and the nitric oxide pathway in [3H]purine outflow evoked by short-term hypoxia and hypoglycemia in rat hippocampal slices.
The objective of this study was to study how the outflow of [3H]purines is altered during a brief period of ischemic-like conditions in superfused hippocampal slices and to show whether it is regulated by P2 purinoceptors and the nitric oxide (NO) pathway. The outflow of [3H]purines increased in response to 5 min of combined hypoxia/hypoglycemia. High performance liquid chromatography analysis verified the efflux of [3H]adenosine-triphosphate, [3H]adenosine-diphosphate, [3H]adenosine-monophosphate, [3H]adenosine, [3H]inosine, and [3H]hypoxanthine in response to ischemic-like conditions. The P2 receptor antagonists suramin and pyridoxal-phosphate-6-azophenyl-2'-4'-disulphonic-acid-tetrasodium (PPADS) reduced significantly the [3H]purine efflux evoked by ischemic-like conditions, showing that P2 purinoceptors are involved in the initiation of purine outflow. The NO synthase inhibitor N-nitro-l-arginine-methyl-ester (l-NAME) attenuated significantly the [3H]purine outflow, evoked by ischemic-like conditions, while 7-nitroindazole (7-NI) caused only a mild decrease in the outflow. The NO donor sodium nitroprusside increased significantly the basal efflux of [3H]purines. In summary, a brief period of combined hypoxia/hypoglycemia induced the efflux of ATP in addition to the outflow of other purines. Since P2 receptor antagonists decreased the [3H]purine outflow evoked by ischemic-like conditions we propose that ATP, acting on P2 purinoceptors, is responsible for further efflux of purines after ischemic-like period. It seems likely that NO is also involved in the regulation of purine outflow, since inhibition of NO production attenuated the [3H]purine outflow, evoked by ischemic-like conditions, while exogenous NO facilitated the basal outflow.
Jurányi
Z
Z
Department of Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, P.O. Box 67, Budapest, H-1450, Hungary.
Sperlágh
B
B
Vizi
E S
ES
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D006624:Hippocampus / Q000378:metabolism*; D007003:Hypoglycemia / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D011687:Purines / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D013997:Time Factors; D014316:Tritium
D011687:Purines; D018048:Receptors, Purinergic P2; D014316:Tritium; D009569:Nitric Oxide; D000255:Adenosine Triphosphate