British journal of pharmacology
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1. Pilocarpine administration has been used as an animal model for temporal lobe epilepsy since it produces several morphological and synaptic features in common with human complex partial seizures. Little is known about changes in extracellular neurotransmitter concentrations during the seizures provoked by pilocarpine, a non-selective muscarinic agonist. 2. ⋯ These are arguments in favour of earlier described NMDA receptor-mediated excitotoxicity. Hippocampal dopamine release may be functionally important in epileptogenesis and may participate in the anticonvulsant effects of MK-801 and lamotrigine. The pilocarpine-stimulated hippocampal GABA, glutamate and dopamine levels reflect neuronal vesicular release.
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1. Peroxynitrite, a potent cytotoxic oxidant formed by the reaction of nitric oxide with superoxide anion, and hydroxyl radical, formed in the iron-catalysed Fenton reaction, are important mediators of reperfusion injury. In in vitro studies, DNA single strand breakage, triggered by peroxynitrite or by hydroxyl radical, activates the nuclear enzyme poly (ADP-ribose) synthetase (PARS), with consequent cytotoxic effects. ⋯ In conclusion, our study demonstrates that the PARS inhibitor 3-aminobenzamide exerts multiple protective effects in splanchnic artery occlusion/reperfusion shock. We suggest that peroxynitrite and/or hydroxyl radical, produced during the reperfusion phase, trigger DNA strand breakage, PARS activation and subsequent cellular dysfunction. The vascular endothelium is likely to represent an important cellular site of protection by 3-aminobenzamide in SAO shock.