Ghrelin potentiates miniature excitatory postsynaptic currents in supraoptic magnocellular neurones.
Ghrelin is an orexigenic peptide discovered in the stomach as a ligand of the orphan G-protein coupled receptor, and participates in the regulation of growth hormone (GH) release. Previous studies have demonstrated that ghrelin suppressed water intake and stimulated the secretion of arginine vasopressin in rats. We examined the effect of ghrelin on the excitatory synaptic inputs to the magnocellular neurosecretory cells (MNCs) in the supraoptic nucleus (SON) using whole-cell patch-clamp recordings in in vitro rat and mouse brain slice preparations. The application of ghrelin (10(-7) approximately 10(-6) m) caused a significant increase in the frequency of the miniature excitatory postsynaptic currents (mEPSCs) in a dose-related manner without affecting the amplitude. The increased frequency of the spontaneous EPSCs persisted in the presence of tetrodotoxin (1 microM). Des-n-octanoyl ghrelin (10(-6) m) did not have a significant effect on the mEPSCs. The ghrelin-induced potentiation of the mEPSCs was significantly suppressed by previous exposure to the transient receptor potential vanilloid (TRPV) blocker, ruthenium red (10 microM) and GH secretagougue type 1a receptor selective antagonist, BIM28163 (10 microM). The effects of ghrelin on the supraoptic MNCs in trpv1 knockout mice were significantly attenuated compared to those in wild-type mice counterparts. These results suggest that ghrelin participates in the regulation of synaptic inputs to the MNCs in the SON via interaction with the GH secretagogue type 1a receptor, and that the TRPV1 channel may be involved in ghrelin-induced potentiation of mEPSCs to the MNCs in the SON.
Yokoyama
T
T
Department of Physiology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
Saito
T
T
Ohbuchi
T
T
Suzuki
H
H
Otsubo
H
H
Okamoto
T
T
Fujihara
H
H
Nagatomo
T
T
Ueta
Y
Y
D000818:Animals; D004305:Dose-Response Relationship, Drug; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects*; D054439:Ghrelin / Q000494:pharmacology*; D066298:In Vitro Techniques; D051379:Mice; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D013495:Supraoptic Nucleus / Q000166:cytology / Q000187:drug effects*
D054439:Ghrelin