title: Role of platelet-activating factor in long-term potentiation of the rat medial vestibular nuclei.
abstract: In rat brain stem slices, we investigated the role of platelet activating factor (PAF) in long-term potentiation (LTP) induced in the ventral part of the medial vestibular nuclei (MVN) by high-frequency stimulation (HFS) of the primary vestibular afferent. The synaptosomal PAF receptor antagonist, BN-52021 was administered before and after HFS. BN-52021 did not modify the vestibular potentials under basal conditions, but it reduced the magnitude of potentiation induced by HFS, which completely developed after the drug wash-out. The same effect was obtained by using CV-62091, a more potent PAF antagonist at microsomal binding sites, but with concentrations higher than those of BN-52021. By contrast both BN-52021 and CV-6209 had no effect on the potentiation once induced. This demonstrates that PAF is involved in the induction but not in the maintenance of vestibular long-term effect through activation of synaptosomal PAF receptors. In addition, we analyzed the effect of the PAF analogue, 1-O-hexadecyl-2-O- (methylcarbamyl)-sn-glycero-3-phosphocoline (MC-PAF) and the inactive PAF metabolite, 1-O-hexadecyl-sn-glycero-3-phosphocoline (Lyso-PAF) on vestibular responses. Our results show that MC-PAF, but not Lyso-PAF induced potentiation. This potentiation was prevented by D,L-2-amino 5-phosphonopentanoic acid, suggesting an involvement of N-methyl-D-aspartate receptors. Furthermore, under BN-52021 and CV-6209, the MC-PAF potentiation was reduced or abolished. The dose-effect curve of MC-PAF showed a shift to the right greater under BN-52021 than under CV-6209, confirming the main dependence of MC-PAF potentiation on the activation of synaptosomal PAF receptors. Our results suggest that PAF can be released in the MVN after the activation of postsynaptic mechanisms triggering LTP, and it may act as a retrograde messenger which activates the presynaptic mechanisms facilitating synaptic plasticity.
authors.affiliation: Institute of Human Physiology, University of Perugia, I-06100 Perugia, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Grassi
authors.forename: E
authors.initials: E
authors.lastname: Francescangeli
authors.forename: G
authors.initials: G
authors.lastname: Goracci
authors.forename: V E
authors.initials: VE
authors.lastname: Pettorossi
mesh_terms: D000818:Animals; D004224:Diterpenes; D046934:Ginkgolides; D066298:In Vitro Techniques; D007783:Lactones / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000502:physiology*; D010972:Platelet Activating Factor / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors; D011726:Pyridinium Compounds / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D009435:Synaptic Transmission / Q000502:physiology; D014726:Vestibular Nuclei / Q000502:physiology*
chemical_list: D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011726:Pyridinium Compounds; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; C053321:CV 6209; C045856:ginkgolide B