title: The effects of CRF and urocortins on the hippocampal glutamate release.
abstract: Corticotropin-releasing factor (CRF) is a hypothalamic neurohormone and an extrahypothalamic neurotransmitter that regulates the hypothalamic-pituitary-adrenal (HPA) axis. The urocortins (UCN I, UCN II and UCN III) are CRF-related peptides, which may also regulate the HPA axis directly or indirectly, by modulation of extrahypothalamic neurotransmitters, such as amygdalar GABA and hippocampal glutamate. Our previous in vitro superfusion studies have already demonstrated that CRF and UCN I stimulate the amygdalar GABA release in rats. The aim of the present study was to investigate the effects of CRF, UCN I, UCN II and UCN III on the glutamate release elicited electrically from rat hippocampal slices in similar in vitro conditions. In order to investigate the participation of CRF receptors (CRFR1 and CRFR2) in this process, hippocampal slices were pretreated with antalarmin, a selective antagonist of CRFR1 or astressin 2B, a selective antagonist of CRFR2. CRF and UCN I at 100 nM decreased significantly the hippocampal glutamate release evoked by electrical stimulation. In contrast, 100 nM of UCN II and UCN III did not affect significantly the hippocampal glutamate release enhanced by electrical stimulation. The decreasing effects of CRF and UCN I were reversed by antalarmin, but not by astressin 2B, both being administered in equimolar doses. Our results demonstrate that CRF and UCN I inhibit the glutamate release in the hippocampus via CRFR1 and that CRFR2 does not participate to this process. Based on the previous and the present results we conclude that CRFR1 agonists can activate the HPA axis not only directly, but also indirectly by increasing the amygdalar GABA release and decreasing the hippocampal glutamate release.
authors.affiliation: Department of Pathophysiology, Faculty of Medicine, University of Szeged, Hungary. Electronic address: bagosi.zsolt@med.u-szeged.hu.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Bagosi
authors.affiliation: Department of Pathophysiology, Faculty of Medicine, University of Szeged, Hungary.
authors.forename: Beáta
authors.initials: B
authors.lastname: Balangó
authors.affiliation: Department of Pathophysiology, Faculty of Medicine, University of Szeged, Hungary.
authors.forename: Dávid
authors.initials: D
authors.lastname: Pintér
authors.affiliation: Department of Pathophysiology, Faculty of Medicine, University of Szeged, Hungary.
authors.forename: Krisztina
authors.initials: K
authors.lastname: Csabafi
authors.affiliation: Department of Pathophysiology, Faculty of Medicine, University of Szeged, Hungary.
authors.forename: Miklós
authors.initials: M
authors.lastname: Jászberényi
authors.affiliation: Department of Pathophysiology, Faculty of Medicine, University of Szeged, Hungary.
authors.forename: Gyula
authors.initials: G
authors.lastname: Szabó
authors.affiliation: Department of Pathophysiology, Faculty of Medicine, University of Szeged, Hungary.
authors.forename: Gyula
authors.initials: G
authors.lastname: Telegdy
mesh_terms: D000679:Amygdala / Q000187:drug effects; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D017208:Rats, Wistar; D054832:Urocortins / Q000494:pharmacology*
chemical_list: D054832:Urocortins; D018698:Glutamic Acid; D003346:Corticotropin-Releasing Hormone
keywords: CRF; Glutamate; HPA axis; Superfusion; Urocortin