guanosine-diphosphate and phenylalanyl-leucyl-phenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide

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).

Topics: Action Potentials; Adamantane; Amino Acid Sequence; Animals; Base Sequence; Biological Clocks; Dipeptides; DNA, Complementary; Dose-Response Relationship, Drug; Female; FMRFamide; Gonadotropin-Releasing Hormone; Guanosine Diphosphate; Ion Transport; Male; Molecular Sequence Data; Neurons; Olfactory Pathways; Oligopeptides; Perciformes; Potassium Channels, Voltage-Gated; Prosencephalon; Receptors, G-Protein-Coupled; Receptors, Neuropeptide; Sequence Homology, Amino Acid; Thionucleotides