Neuropeptide Y5 Receptors Mediate Inhibition of Synaptic Excitation In Proximal Subiculum, But Do Not Suppress Epileptiform Activity in Rat Hippocampal Slices. Melisa W.Y. Ho1,3, Annette G. Beck-Sickinger2,4 and William F. Colmers1. 1Dept. of Pharmacology, Univ. Of Alberta, Edmonton, Alberta, Canada T6G 2H7; 2Dept. of Pharmazie, Swiss Federal Institute, Zurich, Switzerland; 3Present address: Inositide Signaling Section, Laboratory of Signal Transduction, NIEHS, NC 27713; and 4Present Address: Institut of Biochemistry,University of Leipzig, Talstr. 33, D 04103 Leipzig, Germany.
APStracts 6:0531N, 1999.
Neuropeptide Y (NPY) potently inhibits excitatory synaptic transmission in the hippocampus, acting predominantly via a presynaptic Y2 receptor. Recent reports that the Y5 receptor may mediate the anticonvulsant actions of NPY in vivo prompted us to test the hypothesis that Y5 receptors inhibit synaptic excitation in the hippocampal slice and, furthermore, that they are effective in an in vitro model of anticonvulsant action. Two putative Y5 receptor-preferring agonists inhibited excitatory postsynaptic currents (EPSCs) evoked by stimulation of stratum radiatum in pyramidal cells. We recorded initially from area CA1 pyramidal cells, but subsequently switched to cells from the subiculum, where a much greater frequency of response was observed to Y5 agonist application. Both D-Trp32NPY (1 (M) and [ahx8-20]Pro34NPY (3 (M), a centrally-truncated, Y1/Y5 agonist we synthesized, inhibited stimulus-evoked EPSCs in subicular pyramidal cells by 44.0(5.7% and 51.3(3.5%, in 37% and 58% of cells, respectively. By contrast, the less selective centrally-truncated agonist, [ahx8-20] NPY (1 (M), was more potent (66.4(4.1% inhibition), and more widely effective, suppressing the EPSC in 86% of subicular neurons. The site of action of all NPY agonists tested was most probably presynaptic, as agonist application caused no changes in postsynaptic membrane properties. The selective Y1 antagonist, BIBP3226 (1 (M), did not reduce the effect of either more selective agonist, indicating that they activated presynaptic Y5 receptors. Y5 receptor-mediated synaptic inhibition was more frequently observed in slices from younger animals, while the nonselective agonist appeared equally effective at all ages tested. Because of the similarity with the previously-reported actions of Y2 receptors, we tested the ability of Y5 receptor agonists to suppress stimulus train-induced bursting (STIB), an in vitro model of ictaform activity, in both area CA3 and the subiculum. Neither [ahx8-20]Pro34NPY nor D-Trp32NPY were significantly effective in suppressing or shortening STIB induced afterdischarge, with less than 20% of slices responding to these agonists in recordings from CA3 and none in subiculum. By contrast, 1 (M each of [ahx8-20]NPY, the Y2 agonist, [ahx524]NPY, and particularly NPY itself suppressed the afterdischarge in area CA3 and the subiculum, as reported earlier . We conclude that Y5 receptors appear to regulate excitability to some degree in the subiculum of young rats but their contribution is relatively small compared with those of Y2 receptors, declines with age, and is insufficient to block or significantly attenuate STIB-induced afterdischarges.
Received 2 April 1999; accepted in final form 18 October 1999.
APS Manuscript Number J293-9.
Article publication pending Journal of Neurophysiology.
ISSN 1080-4757 Copyright 1999 The American Physiological Society.
Published in APStracts on 21 December 1999