In vivo regulation of extracellular adenosine levels in the cerebral cortex by NMDA and muscarinic receptors.
The adenosine concentration in samples of perfusate was determined 24 h after implantation of microdialysis fibre in the cortex. High performance liquid chromatography coupled with a fluorometric detector was used. K+ (100 mM) depolarization was followed by a 2- to 4-fold increase in adenosine efflux. The addition of tetrodotoxin (1 microM) to the perfusate was followed by a decrease in spontaneous and K(+)-evoked adenosine efflux. The increase induced by high K+ was markedly inhibited by the NMDA receptor antagonist, D(-)-2-amino-7-phosphonoheptanoic acid (1 mM, D-AP7), but not by the muscarinic receptor antagonist, atropine (1.5 microM). The acetylcholine esterase inhibitor, physostigmine (7 microM), and the muscarinic receptor agonist, oxotremorine (100 microM), significantly enhanced the K(+)-evoked increase in adenosine. The spontaneous efflux of adenosine was not modified by any of the drugs tested. A neurotoxic lesion of the cholinergic pathway innervating the cortex, although inducing a marked decrease in cortical choline acetyltransferase activity, did not significantly modify the cortical adenosine efflux. It is concluded that, under K(+)-depolarizing conditions, adenosine efflux is triggered by excitatory amino acids and enhanced by muscarinic activation.
Department of Preclinical and Clinical Pharmacology, University of Florence, Italy.
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Pazzagli
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Latini
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Pedata
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Pepeu
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives*; D000241:Adenosine / Q000032:analysis / Q000378:metabolism*; D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D008297:Male; D010095:Oxotremorine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*
D000596:Amino Acids; D011976:Receptors, Muscarinic; D016194:Receptors, N-Methyl-D-Aspartate; D010095:Oxotremorine; D015763:2-Amino-5-phosphonovalerate; D000241:Adenosine; C031231:2-amino-7-phosphonoheptanoic acid; D011188:Potassium