title: Neuropeptide FF (NPFF) control of magnocellular neurosecretory cells of the rat hypothalamic paraventricular nucleus (PVN).
abstract: Neuropeptide FF (NPFF) is an octapeptide belonging to an extended family of RF amide peptides that have been implicated in a wide variety of physiological functions in the brain. NPFF and its receptors are abundantly expressed in the rat brain and spinal cord including the hypothalamic paraventricular nucleus (PVN), an autonomic nucleus critical for the secretion of neurohormones and the regulation of sympathetic outflow. In this study, we sought to examine the effects of NPFF on GABAergic inhibitory synaptic input to magnocellular neurosecretory cells (MNCs) of the PVN, which secrete the neurohormones, vasopressin and oxytocin from their terminals in the neurohypophysis. Whole cell patch clamp recordings under voltage clamp conditions were performed from PVN MNCs in the brain slice. Bicuculline-sensitive inhibitory postsynaptic currents (IPSCs) were isolated in the presence of glutamate receptor blockers. In tetrodotoxin, NPFF (5 microM) caused an increase in frequency, but not amplitude of miniature inhibitory postsynaptic currents (mIPSCs) in MNCs indicating a presynaptic locus of action for this peptide. Intracerebroventricular application of NPFF resulted in an activation of GABAergic neurons located adjacent to the PVN as revealed by immunohistochemistry for Fos protein and in situ hybridization for glutamic acid decarboxylase (GAD67) mRNA. Based on these observations we conclude that NPFF facilitates inhibitory input to MNCs of the PVN via GABAergic interneurons located in immediate vicinity of the nucleus. These findings provide a cellular and anatomic basis for the NPFF-induced inhibition of vasopressin release has been reported consequent to hypovolemia and hyperosmolar stimulation.
authors.affiliation: Department of Medicine (Neurology) and Centre for Neuroscience, University of Alberta, Edmonton, Alta., Canada T6G 2B7. jack.jhamandas@ualberta.ca
authors.forename: Jack H
authors.initials: JH
authors.lastname: Jhamandas
authors.forename: David
authors.initials: D
authors.lastname: MacTavish
authors.forename: Kim H
authors.initials: KH
authors.lastname: Harris
mesh_terms: D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005968:Glutamate Decarboxylase / Q000096:biosynthesis; D007276:Injections, Intraventricular; D007527:Isoenzymes / Q000096:biosynthesis; D007736:Kynurenic Acid / Q000494:pharmacology; D008297:Male; D009490:Neurosecretory Systems / Q000166:cytology / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology / Q000502:physiology*; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology* / Q000502:physiology; D018408:Patch-Clamp Techniques; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D007527:Isoenzymes; D009842:Oligopeptides; D016760:Proto-Oncogene Proteins c-fos; D011963:Receptors, GABA-A; D013779:Tetrodotoxin; C053651:phenylalanyl-leucyl-phenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; D007736:Kynurenic Acid; D001640:Bicuculline