Activation of A(3) receptors by endogenous adenosine inhibits synaptic transmission during hypoxia in rat cortical neurons.
OBJECTIVE
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%N(2)-5%CO(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 N(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-beta-S).


CONCLUSIONS
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.
Hentschel
S
S
Institute of Pharmacy, Pharmacology for Natural Sciences, University of Leipzig, Germany.
Lewerenz
A
A
Nieber
K
K
D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives / Q000378:metabolism*; D000818:Animals; D015687:Cell Hypoxia; D002540:Cerebral Cortex / Q000166:cytology*; D004347:Drug Interactions; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006151:Guanosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D017966:Pyramidal Cells / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D043684:Receptor, Adenosine A3; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013872:Thionucleosides / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D013997:Time Factors
D004791:Enzyme Inhibitors; D014179:Neurotransmitter Uptake Inhibitors; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D043684:Receptor, Adenosine A3; D018047:Receptors, Purinergic P1; D013872:Thionucleosides; D013873:Thionucleotides; D006151:Guanosine; C002121:6-(4-nitrobenzylthio)guanosine; D006153:Guanosine Diphosphate; C010192:9-(2-hydroxy-3-nonyl)adenine; C023427:guanosine 5'-O-(2-thiodiphosphate); D000225:Adenine; D000241:Adenosine