ISSN:
1460-9568
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Neuropeptide Y (NPY) potently inhibits glutamate release and seizure activity in rodent hippocampus in vitro and in vivo, but the nature of the receptor(s) mediating this action is controversial. In hippocampal slices from rats and several wild-type mice, a Y2-preferring agonist mimicked, and the Y2-specific antagonist BIIE0246 blocked, the NPY-mediated inhibition both of glutamatergic transmission and of epileptiform discharges in two different slice models of temporal lobe epilepsy, stimulus train-induced bursting (STIB) and 0-Mg2+ bursting. Whereas Y5 receptor-preferring agonists had small but significant effects in vitro, they were blocked by BIIE0246, and a Y5 receptor-specific antagonist did not affect responses to any agonist tested in any preparation. In slices from 〈inlineGraphic alt="inline image" href="urn:x-wiley:0953816X:EJN4338:EJN_4338_mu1" location="equation/EJN_4338_mu1.gif"/〉 mice, NPY was without effect on evoked potentials or in either of the two slice seizure models. In vivo, intrahippocampal injections of Y2- or Y5-preferring agonists inhibited seizures caused by intrahippocampal kainate, but again the Y5 agonist effects were insensitive to a Y5 antagonist. Neither Y2- nor Y5-preferring agonists affected kainate seizures in 〈inlineGraphic alt="inline image" href="urn:x-wiley:0953816X:EJN4338:EJN_4338_mu2" location="equation/EJN_4338_mu2.gif"/〉 mice. A Y5-specific antagonist did not displace the binding of two different NPY ligands in WT or 〈inlineGraphic alt="inline image" href="urn:x-wiley:0953816X:EJN4338:EJN_4338_mu3" location="equation/EJN_4338_mu3.gif"/〉 mice, whereas all NPY binding was eliminated in the 〈inlineGraphic alt="inline image" href="urn:x-wiley:0953816X:EJN4338:EJN_4338_mu4" location="equation/EJN_4338_mu4.gif"/〉 mouse. Thus, we show that Y2 receptors alone mediate all the anti-excitatory actions of NPY seen in the hippocampus, whereas our findings do not support a role for Y5 receptors either in vitro or in vivo. The results suggest that agonists targeting the Y2 receptor may be useful anticonvulsants.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1460-9568.2005.04338.x
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