title: Effective G-protein coupling of Y2 receptors along axonal fiber tracts and its relevance for epilepsy.
abstract: Neuropeptide Y (NPY)-Y2 receptors are G-protein coupled receptors and, upon activation, induce opening of potassium channels or closing of calcium channels. They are generally presynaptically located. Depending on the neuron in which they are expressed they mediate inhibition of release of NPY and of the neuron's classical transmitter GABA, glutamate or noradrenaline, respectively. Here we provide evidence that Y2 receptor binding is inhibited dose-dependently by GTPγS along Schaffer collaterals, the stria terminalis and the fimbria indicating that Y2 receptors are functionally coupled to G-proteins along these fiber tracts. Double immune fluorescence revealed coexistence of Y2-immunoreactivity with β-tubulin, a marker for axons in the stria terminalis, but not with synaptophysin labeling presynaptic terminals, supporting the localization of Y2 receptors along axonal tracts. After kainic acid-induced seizures in rats, GTPγS-induced inhibition of Y2 receptor binding is facilitated in the Schaffer collaterals but not in the stria terminalis. Our data indicate that Y2 receptors are not only located at nerve terminals but also along fiber tracts and are there functionally coupled to G-proteins.
authors.affiliation: Department of Pharmacology, Innsbruck Medical University, Peter-Mayr-Str. 1a, 6020 Innsbruck, Austria. Electronic address: dum.elisabeth@gmail.com.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Dum
authors.affiliation: Department of Pharmacology, Innsbruck Medical University, Peter-Mayr-Str. 1a, 6020 Innsbruck, Austria. Electronic address: sabine.fuertinger@gmx.at.
authors.forename: Sabine
authors.initials: S
authors.lastname: Fürtinger
authors.affiliation: Department of Pharmacology, Innsbruck Medical University, Peter-Mayr-Str. 1a, 6020 Innsbruck, Austria.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Gasser
authors.affiliation: Department of Pharmacology, Innsbruck Medical University, Peter-Mayr-Str. 1a, 6020 Innsbruck, Austria.
authors.forename: Anneliese
authors.initials: A
authors.lastname: Bukovac
authors.affiliation: Department of Pharmacology, Innsbruck Medical University, Peter-Mayr-Str. 1a, 6020 Innsbruck, Austria.
authors.forename: Meinrad
authors.initials: M
authors.lastname: Drexel
authors.affiliation: Department of Pharmacology, Innsbruck Medical University, Peter-Mayr-Str. 1a, 6020 Innsbruck, Austria.
authors.forename: Ramon
authors.initials: R
authors.lastname: Tasan
authors.affiliation: Department of Pharmacology, Innsbruck Medical University, Peter-Mayr-Str. 1a, 6020 Innsbruck, Austria. Electronic address: guenther.sperk@i-med.ac.at.
authors.forename: Günther
authors.initials: G
authors.lastname: Sperk
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D007608:Kainic Acid; D008297:Male; D009412:Nerve Fibers / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017476:Receptors, Neuropeptide Y / Q000378:metabolism*; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism*; D016708:Synaptophysin / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism
chemical_list: D017476:Receptors, Neuropeptide Y; D016708:Synaptophysin; D014404:Tubulin; C095889:neuropeptide Y2 receptor; D019204:GTP-Binding Proteins; D007608:Kainic Acid
keywords: Epilepsy; G-protein coupling; GTPγS; Kainic acid; NPY; Schaffer collaterals; Stria terminalis; Y2 receptors