Neuropeptide Y suppresses epileptiform activity in rat frontal cortex and hippocampus in vitro via different NPY receptor subtypes.
Neuropeptide Y (NPY) and different NPY receptor (Y) subtype-selective agonists were tested for their effects on spontaneous epileptiform discharges which developed in rat cortical and hippocampal slices in Mg(2+)-free medium. Epileptiform activity, recorded extracellularly, was attenuated by NPY (0.5-1 microM) in both the frontal cortex and hippocampal CA3/CA1 pyramidal cell layers. In the cortex the Y1/5 selective agonist [Leu31 Pro34] NPY was more effective than the Y2 preferring agonist NPY13-36 and the Y2/5 preferring agonist NPY3-36. The suppression of epileptiform discharges induced by NPY in cortical slices was blocked by the selective Y1 receptor antagonist (R)-N2-(diphenylacetyl)-N-((4-hydroxyphenyl)methyl] argininamide (BIBP 3226). In the hippocampus, NPY13-36 and NPY3-36 were more effective than [Leu31 Pro34] NPY. In conclusion, the antiepileptic activity of NPY is mediated predominantly by the Y1 receptor subtype in the frontal cortex and by Y2 and probably Y5 receptors in the hippocampal CA3/CA1 areas.
Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland. nfbijak@cyf-kr.edu.pl
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D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects*; D005071:Evoked Potentials / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects; D008297:Male; D009478:Neuropeptide Y / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017476:Receptors, Neuropeptide Y / Q000819:agonists* / Q000187:drug effects*
D000927:Anticonvulsants; C092926:BIBP 3226; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; C095889:neuropeptide Y2 receptor; D001120:Arginine