Affiliations: Institute of Pharmacy, Pharmacology for Natural
Sciences, University of Leipzig, Germany
Note: [] Corresponding author: Dr. Karen Nieber, Universität
Leipzig, Institut für Pharmazie, Liebigstr. 18, D-04103 Leipzig, Germany.
Tel.: +49 341 9736812; Fax: +49 341 9736889; E-mail: nieber@ rz.uni-leipzig.de
Abstract: Purpose: The aim of our study was to characterize the influence of
A_3 receptors on synaptic potentials (PSPs) in pyramidal
cells from the rat cingulate cortex during hypoxia. METHODS: Intracellular
recordings ($n=49$) were taken from slice preparations. PSPs were evoked by
electrical stimulation. Results: Hypoxia
(95%NA_2-5%COA_2, 5 min) reduced the
amplitude of the PSPs significantly. The effect was more pronounced in the
presence of adenosine re-uptake inhibitor S-(p-nitrobenzyl)-6-thioguanosine
(NBTG) and deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA); the
effect was completely reversed by bovine adenosine deaminase. Hypoxic
inhibition induced after A_1 receptor blockade with
1,3-dipropyl-8-cyclopentylxanthine (DPCPX) in the presence of NBTG was
completely reversed by the A_3 antagonist
9-chloro-2-(2-furanyl)-5-[(phenylacetyl)amino]-1,2,4-triazolo[1,5-c]quinazoline
(MRS 1220), indicating the involvement of A_3 receptors in
hypoxic PSP inhibition. This was confirmed by A_3 agonist
NA^6-(3-iodobenzyl)-adenosine-5'-N-methylcarboxamide
(IB-MECA) inhibiting PSPs. The effect of IB-MECA was blocked by the rat
A_3 receptor-selective antagonist
3-propyl-6-ethyl-5-[(ethylthio)carbonyl]-2-phenyl-4-propyl-3-pyridinecarboxylate
(MRS 1523) and was not observed in the presence of G-protein inhibitor
guanosine-5'-O-2-thiodiphosphate (GDP-β-S). Conclusion: We conclude that a high level of endogenous adenosine,
which occurs during hypoxia, activates A_3 receptors. Their
activation contributes to PSP inhibition by adenosine during hypoxia.
