title: Opposite modulation of 4-aminopyridine and hypoxic hyperexcitability by A1 and A2 adenosine receptor ligands in rat hippocampal slices.
abstract: The effects of the adenosine receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), and of the adenosine agonists N6-cyclopentyladenosine (CPA), N6-(2-phenylisopropyl)adenosine (R-PIA), and 2-[p-(carboxyethyl)phenylethylamino]-5'-N-ethylcarboxamidoadenosin e (CGS 21680) were investigated on the hyperexcitability induced in the CA1 area of rat hippocampal slices by hypoxia or the epileptogenic agent 4-aminopiridine. Slice perfusion with the mixed adenosine receptor agonist R-PIA (0.2 microM) significantly (P < 0.05) decreased: (i) the number of slices showing a transient CA1 epileptiform bursting during the hypoxic period; (ii) the duration of the hypoxia-induced epileptiform bursting. Conversely, slice perfusion with the selective A1 adenosine receptor antagonists DPCPX (0.2 microM) or with the selective A2 adenosine receptor agonist CGS 21680 significantly (P < 0.05) increased the number of slices showing a transient CA1 epileptiform bursting during the hypoxic period but did not affect the duration of the hypoxia-induced epileptiform bursting. Neither drug significantly affected the number of slices showing functional recovery after hypoxia. Slice perfusion with DPCPX (0.2 microM) also significantly increased (P < 0.05) the number of slices showing a persistent CA1 epileptiform bursting during the reoxygenation period, while the other drugs failed to affect it. Slice perfusion with the selective A1 adenosine receptor agonist CPA (2 microM) or R-PIA (5 microM) significantly (P < 0.05) decreased the duration of the CA1 epileptiform bursting induced by 100 microM 4-aminopyridine. CGS 21680 (5 microM) perfused together with CPA (2 microM) significantly (P < 0.05) counteracted the inhibitory effects of the A1 adenosine receptor agonist on 4-aminopyridine epileptiform bursting, while it failed by itself to directly affect the 4-aminopyridine epileptiform bursting duration. The results produce evidence for a selective opposite modulation by A1 and A2 adenosine agonists in the control of hippocampal hyperexcitability induced by hypoxia or 4-aminopyridine but not in the post-hypoxic functional recovery.
authors.affiliation: Laboratorio di Farmacologia, Istituto Superiore Di Sanità, Roma, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Longo
authors.forename: Y C
authors.initials: YC
authors.lastname: Zeng
authors.forename: S
authors.initials: S
authors.lastname: Sagratella
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology*; D000818:Animals; D004827:Epilepsy / Q000139:chemically induced; D006624:Hippocampus / Q000187:drug effects*; D000860:Hypoxia / Q000378:metabolism*; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D018047:Receptors, Purinergic P1 / Q000187:drug effects*; D013997:Time Factors
chemical_list: D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D015761:4-Aminopyridine