Effect of the pyridoindole SMe1EC2 and compounds affecting A(1) and A(2A) adenosine receptors in rat hippocampus under ischemia in vitro.

Abstract

The effect of the newly synthesized pyridoindole antioxidant SMe1EC2 (1 micromol/l) and drugs activating or inhibiting adenosine receptors was tested under ischemia. Synaptic transmission was recorded extracellularly before and under 6-min ischemia and 20-min reoxygenation in rat hippocampal slices in vitro. In untreated slices, ischemia elicited failure of synaptic transmission and excitability expressed by a population spike decay (t(0.5) = 1.7 +/- 0.1 min) and poor recovery of synaptic transmission at the end of reoxygenation, expressed as percentage of PoS amplitude of that at zero minute of ischemia (9.9 +/- 3.6%). The compound SMe1EC2 increased recovery of PoS amplitude in reoxygenation (31.2 +/- 7.0% of that at the beginning of ischemia) and decreased the number of irreversibly damaged slices in reoxygenation (64%) compared to untreated slices (80%). Co-administration of SMe1EC2 + SCH-58261 (1 micromol/l, A(2A) adenosine receptor antagonist) resulted in delayed synaptic transmission decay during 6-min ischemia (t(0.5) = 2.3 +/- 0.1 min), increased PoS amplitude recovery during reoxygenation (37.7 +/- 12.4% of that at zero minute of ischemia), and in a decreased number of slices with damaged synaptic transmission at the end of reoxygenation (54%), all data compared to untreated controls. Co-administration of pyridoindole with CGS 21680 (1 micromol/l, A(2A) adenosine receptor agonist) or with DPCPX (100 nmol/l, A(1) adenosine receptor antagonist) eliminated the described effect. Further studies are required to elucidate the putative influence of manipulation with adenosine receptors on the neuroprotective effect of SMe1EC2 under ischemia.

• Authors: Zdenka Gáspárová, Pavol Jariabka, Svorad Stolc
• Journal: Pharmacological reports : PR (Pharmacol Rep) 2008 May-Jun Vol. 60 Issue 3 Pg. 353-60 ISSN: 1734-1140 [Print] Switzerland
• PMID: 18622060 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine
• Adenosine A1 Receptor Agonists
• Adenosine A1 Receptor Antagonists
• Adenosine A2 Receptor Agonists
• Adenosine A2 Receptor Antagonists
• Antioxidants
• Indoles
• Neuroprotective Agents
• Phenethylamines
• Pyridines
• Pyrimidines
• Receptor, Adenosine A1
• Receptor, Adenosine A2A
• SMe1EC2
• Triazoles
• Xanthines
• 2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine
• N(6)-cyclopentyladenosine
• 1,3-dipropyl-8-cyclopentylxanthine
• Adenosine
• Oxygen

Topics

• Action Potentials (drug effects, physiology)
• Adenosine (analogs & derivatives, pharmacology)
• Adenosine A1 Receptor Agonists
• Adenosine A1 Receptor Antagonists
• Adenosine A2 Receptor Agonists
• Adenosine A2 Receptor Antagonists
• Animals
• Antioxidants (chemistry, pharmacology)
• Dose-Response Relationship, Drug
• Electrophysiology
• Hippocampus (drug effects, physiopathology)
• Hypoxia (physiopathology)
• Hypoxia-Ischemia, Brain (physiopathology)
• In Vitro Techniques
• Indoles (chemistry, pharmacology, therapeutic use)
• Male
• Neuroprotective Agents (chemistry, pharmacology)
• Oxygen (metabolism)
• Phenethylamines (pharmacology)
• Pyridines (chemistry, pharmacology, therapeutic use)
• Pyrimidines (pharmacology)
• Rats
• Rats, Wistar
• Receptor, Adenosine A1 (physiology)
• Receptor, Adenosine A2A (physiology)
• Synaptic Transmission (drug effects, physiology)
• Time Factors
• Triazoles (pharmacology)
• Xanthines (pharmacology)