Abstract
Receptor autoradiography with the Y2 receptor ligand125I-peptide YY3–36 and in situhybridization were applied to investigate changes in neuropeptide tyrosine-Y2 receptor expression after kainic acid-induced recurrent seizures in the rat hippocampus. In the strata oriens and radiatum of CA1 to CA3, which are densely innervated by Y2receptor-bearing Schaffer collateral terminals, a transient 2-fold increase in Y2 receptor affinity was observed after 4–12 hr, with a later slow decline. No change was seen in Y2mRNA expression in CA2/CA3 pyramidal cells, from which Schaffer collaterals originate. Conversely, in granule cells of the dentate gyrus, markedly elevated Y2 mRNA concentrations were observed (by 740% in the dorsal hippocampus) 24–48 hr after kainate injection. At the same time, a marked and lasting (up to 6 months) increase in the number of Y2 receptor sites (by 800%) was seen in the dentate hilus, which is innervated densely by mossy fibers. The early increase in Y2 receptor affinity in Schaffer collaterals was accompanied by a 60% decrease in the EC50of peptide YY3–36 in inhibiting K+-stimulated glutamate release in hippocampal slices from kainic acid-treated rats. Our data indicate transient up-regulation of presynaptic Y2receptors in Schaffer collaterals by a change in affinity and a permanent de novo synthesis of presynaptic Y2 receptors in granule cells/mossy fibers. These changes may cause augmented presynaptic inhibition of glutamate release from different hippocampal sites and, in conjunction with increased concentrations of neuropeptide tyrosine in mossy fibers, may represent an endogenous reactive anticonvulsant mechanism.
Footnotes
- Received June 30, 1997.
- Accepted September 13, 1997.
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Send reprint requests to: Dr. Günther Sperk, Department of Pharmacology, Peter-Mayr-Str. 1a, 6020 Innsbruck, Austria. E-mail:guenther.sperk{at}uibk.ac.at
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This work was supported by the Austrian Scientific Research Foundation and the Dr. Legerlotz-Foundation.
- The American Society for Pharmacology and Experimental Therapeutics
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