title: 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.affiliation: Institute of Experimental Pharmacology, Slovak Academy of Sciences, Dubravska cesta 9, 841 04 Bratislava, Slovak Republic. exfagasp@savba.sk
authors.forename: Zdenka
authors.initials: Z
authors.lastname: Gáspárová
authors.forename: Pavol
authors.initials: P
authors.lastname: Jariabka
authors.forename: Svorad
authors.initials: S
authors.lastname: Stolc
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D058907:Adenosine A1 Receptor Agonists; D058916:Adenosine A1 Receptor Antagonists; D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology*; D020925:Hypoxia-Ischemia, Brain / Q000503:physiopathology; D066298:In Vitro Techniques; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism; D010627:Phenethylamines / Q000494:pharmacology; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043682:Receptor, Adenosine A1 / Q000502:physiology*; D043705:Receptor, Adenosine A2A / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D014230:Triazoles / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
chemical_list: C098657:5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine; D058907:Adenosine A1 Receptor Agonists; D058916:Adenosine A1 Receptor Antagonists; D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D000975:Antioxidants; D007211:Indoles; D018696:Neuroprotective Agents; D010627:Phenethylamines; D011725:Pyridines; D011743:Pyrimidines; D043682:Receptor, Adenosine A1; D043705:Receptor, Adenosine A2A; C534359:SMe1EC2; D014230:Triazoles; D014970:Xanthines; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C048599:N(6)-cyclopentyladenosine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine; D010100:Oxygen