Electrophysiological analysis of the inhibitory effects of FMRFamide-like peptides on the pacemaker activity of gonadotropin-releasing hormone neurons.
Gonadotropin-releasing hormone (GnRH) neurons in the terminal nerve (TN) show endogenous pacemaker activity, which is suggested to be dependent on the physiological conditions of the animal. The TN-GnRH neurons have been suggested to function as a neuromodulatory neuron that regulates long-lasting changes in the animal behavior. It has been reported that the TN-GnRH neurons are immunoreactive to FMRFamide. Here, we find that the pacemaker activity of TN-GnRH neuron is inhibited by FMRFamide: bath application of FMRFamide decreased the frequency of pacemaker activity of TN-GnRH neurons in a dose-dependent manner. This decrease was suppressed by a blockage of G protein-coupled receptor pathway by GDP-β-S. In addition, FMRFamide induced an increase in the membrane conductance, and the reversal potential for the FMRFamide-induced current changed according to the changes in [K(+)](out) as predicted from the Nernst equation for K(+). We performed cloning and sequence analysis of the PQRFamide (NPFF/NPAF) gene in the dwarf gourami and found evidence to suggest that FMRFamide-like peptide in TN-GnRH neurons of the dwarf gourami is NPFF. NPFF actually inhibited the pacemaker activity of TN-GnRH neurons, and this inhibition was blocked by RF9, a potent and selective antagonist for mammalian NPFF receptors. These results suggest that the activation of K(+) conductance by FMRFamide-like peptide (≈NPFF) released from TN-GnRH neurons themselves causes the hyperpolarization and then inhibition of pacemaker activity in TN-GnRH neurons. Because TN-GnRH neurons make tight cell clusters in the brain, it is possible that FMRFamide-like peptides released from TN-GnRH neurons negatively regulates the activities of their own (autocrine) and/or neighboring neurons (paracrine).
Dept. of Biological Sciences, Graduate School of Science, Univ. of Tokyo, 7-3-1 Hongo, Bukyo-ku, Tokyo 113-0033, Japan.
Takeshi H
TH
Saito
Ryo
R
Nakane
Yasuhisa
Y
Akazome
Hideki
H
Abe
Yoshitaka
Y
Oka
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000218:Adamantane / Q000031:analogs & derivatives / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001683:Biological Clocks / Q000502:physiology*; D018076:DNA, Complementary / Q000235:genetics; D004151:Dipeptides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019835:FMRFamide / Q000494:pharmacology; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D017136:Ion Transport / Q000187:drug effects / Q000502:physiology; D008297:Male; D008969:Molecular Sequence Data; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009833:Olfactory Pathways / Q000166:cytology / Q000502:physiology; D009842:Oligopeptides / Q000235:genetics / Q000502:physiology*; D010473:Perciformes / Q000235:genetics / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects / Q000502:physiology; D016548:Prosencephalon / Q000166:cytology* / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects / Q000502:physiology; D018013:Receptors, Neuropeptide / Q000187:drug effects* / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D013873:Thionucleotides / Q000494:pharmacology
D018076:DNA, Complementary; D004151:Dipeptides; D009842:Oligopeptides; D024642:Potassium Channels, Voltage-Gated; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; D013873:Thionucleotides; C508361:adamantylcarbonyl-arginyl-phenylalaninamide; C083929:neuropeptide FF receptor; D006153:Guanosine Diphosphate; D007987:Gonadotropin-Releasing Hormone; D019835:FMRFamide; C023427:guanosine 5'-O-(2-thiodiphosphate); C053651:phenylalanyl-leucyl-phenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide; D000218:Adamantane