title: Transient and selective blockade of adenosine A1-receptors by 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) causes sustained epileptiform activity in hippocampal CA3 neurons of guinea pigs.
abstract: The effects of endogenously released adenosine on the excitability of hippocampal neurons were studied using the novel and highly selective adenosine A1-receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). Extra- and intracellular recordings performed in area CA1 and CA3 of the guinea pig hippocampal slice preparation revealed that a transient suppression of an inhibitory purinergic tonus by DPCPX leads to sustained interictal-like epileptiform activity arising in area CA3. Once induced, the spontaneous burst discharges were apparently irreversible within the observation period, even after prolonged washout (2-3 h) in normal solution. In contrast, the hyperpolarizing action of exogenous adenosine, which was substantially reduced by DPCPX, recovered within 30-60 min of drug washout, indicating that DPCPX was not irreversibly bound to the A1-receptor.
authors.affiliation: Physiologisches Institut der Universität, Munich, F.R.G.
authors.forename: C
authors.initials: C
authors.lastname: Alzheimer
authors.forename: B
authors.initials: B
authors.lastname: Sutor
authors.forename: G
authors.initials: G
authors.lastname: ten Bruggencate
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D003292:Convulsants / Q000494:pharmacology*; D004827:Epilepsy / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D066298:In Vitro Techniques; D011983:Receptors, Purinergic / Q000187:drug effects / Q000502:physiology*; D014970:Xanthines / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D003292:Convulsants; D011983:Receptors, Purinergic; D014970:Xanthines; C051360:1,3-dipropyl-8-cyclopentylxanthine; D001640:Bicuculline