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.
