title: The hippocampal cholinergic neurostimulating peptide, the N-terminal fragment of the secreted phosphatidylethanolamine-binding protein, possesses a new biological activity on cardiac physiology.
abstract: Phosphatidylethanolamine-binding protein (PEBP), alternatively named Raf-1 kinase inhibitor protein, is the precursor of the hippocampal cholinergic neurostimulating peptide (HCNP) corresponding to its natural N-terminal fragment, previously described to be released by hippocampal neurons. PEBP is a soluble cytoplasmic protein, also associated with plasma and reticulum membranes of numerous cell types. In the present report, using biochemistry and cell biology techniques, we report for the first time the presence of PEBP in bovine chromaffin cell, a well described secretion model. We have examined its presence at the subcellular level and characterized this protein on both secretory granule membranes and intragranular matrix. In addition, its presence in bovine chromaffin cell and platelet exocytotic medium, as well as in serum, was reported showing that it is secreted. Like many other proteins that lack signal sequence, PEBP may be secreted through non-classic signal secretory mechanisms, which could be due to interactions with granule membrane lipids and lipid rafts. By two-dimensional liquid chromatography-tandem mass spectrometry, HCNP was detected among the intragranular matrix components. The observation that PEBP and HCNP were secreted with catecholamines into the circulation prompted us to investigate endocrine effects of this peptide on cardiovascular system. By using as bioassay an isolated and perfused frog (Rana esculenta) heart preparation, we show here that HCNP acts on the cardiac mechanical performance exerting a negative inotropism and counteracting the adrenergic stimulation of isoproterenol. All together, these data suggest that PEBP and HCNP might be considered as new endocrine factors involved in cardiac physiology.
authors.affiliation: INSERM Unité 575, Physiopathologie du Système Nerveux, IFR 37, 67084 Strasbourg, France.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Goumon
authors.forename: Tommaso
authors.initials: T
authors.lastname: Angelone
authors.forename: Françoise
authors.initials: F
authors.lastname: Schoentgen
authors.forename: Sylvette
authors.initials: S
authors.lastname: Chasserot-Golaz
authors.forename: Bjorg
authors.initials: B
authors.lastname: Almas
authors.forename: Miriam M
authors.initials: MM
authors.lastname: Fukami
authors.forename: Keith
authors.initials: K
authors.lastname: Langley
authors.forename: Ingeborg D
authors.initials: ID
authors.lastname: Welters
authors.forename: Bruno
authors.initials: B
authors.lastname: Tota
authors.forename: Dominique
authors.initials: D
authors.lastname: Aunis
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Metz-Boutigue
mesh_terms: D000727:Androgen-Binding Protein; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D015153:Blotting, Western; D002352:Carrier Proteins / Q000737:chemistry*; D002417:Cattle; D019439:Chromaffin Cells; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D003593:Cytoplasm / Q000378:metabolism; D006321:Heart / Q000502:physiology; D007150:Immunohistochemistry; D008055:Lipids / Q000737:chemistry; D013058:Mass Spectrometry; D018613:Microscopy, Confocal; D016253:Microscopy, Immunoelectron; D009206:Myocardium / Q000378:metabolism; D009479:Neuropeptides / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry; D049294:Phospholipid Transfer Proteins; D017434:Protein Structure, Tertiary; D011898:Ranidae; D013347:Subcellular Fractions / Q000378:metabolism; D013997:Time Factors
chemical_list: D000727:Androgen-Binding Protein; D002352:Carrier Proteins; D008055:Lipids; D009479:Neuropeptides; D010455:Peptides; D049294:Phospholipid Transfer Proteins; C075274:hippocampal cholinergic neurostimulating peptide