title: Inhibitory influence of chromogranin A N-terminal fragment (vasostatin-1) on the spontaneous contractions of rat proximal colon.
abstract: Very little is known about the role played by CGA and its fragments in the gastrointestinal physiology. We have studied the role of CGA N-terminal fragments in the regulation of intestinal smooth muscle contractility by measuring the influence of recombinant CGA 1-78 (VS-1) and synthetic CGA 7-57 peptides on the spontaneous mechanical activity of rat proximal colon in vitro. The mechanical activity was recorded as changes in the intraluminal pressure. VS-1 (0.1-30 nM) and CGA 7-57 (10-300 nM) produced concentration-dependent inhibitory effects, characterized by a progressive decrease in the mean amplitude of circular muscle spontaneous contractions, without affecting the resting tone. The response to VS-1 was antagonised by anti-CGA monoclonal antibodies (mAb5A8, B4E11, 7D1 or 4D5) but not by an irrelevant antibody, indicating that the effect was specific. The inhibitory responses to VS-1 and to CGA 7-57 were significantly reduced by pre-treatment of the preparations with N(omega)-nitro-l-arginine methyl ester (l-NAME) (300 microM), 1H-(1,2,4) oxadiazolo-(4,3-a) quinoxalin-1-one (ODQ) (10 microM), apamin (0.1 microM) or tetrodotoxin (TTX) (1 microM). The results suggest that VS-1 plays an inhibitory modulatory role on spontaneous contractions rat colon circular muscle, through mechanisms involving in part neural release of nitric oxide.
authors.affiliation: Dipartimento di Biologia cellulare e dello Sviluppo, Laboratorio di Fisiologia generale Università di Palermo, Viale delle Scienze, 90128 Palermo, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Amato
authors.forename: Angelo
authors.initials: A
authors.lastname: Corti
authors.forename: Rosa
authors.initials: R
authors.lastname: Serio
authors.forename: Flavia
authors.initials: F
authors.lastname: Mulè
mesh_terms: D000818:Animals; D001030:Apamin / Q000494:pharmacology; D037282:Calreticulin / Q000494:pharmacology; D053379:Chromogranin A; D002864:Chromogranins / Q000737:chemistry* / Q000494:pharmacology; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D041981:Gastrointestinal Tract / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D010069:Oxadiazoles / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000737:chemistry; D011312:Pressure; D017434:Protein Structure, Tertiary; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000737:chemistry; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
chemical_list: C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D037282:Calreticulin; D053379:Chromogranin A; D002864:Chromogranins; D004791:Enzyme Inhibitors; D010069:Oxadiazoles; D010446:Peptide Fragments; D010455:Peptides; D011810:Quinoxalines; D011994:Recombinant Proteins; C505867:chromogranin A (1-78); C499788:chromogranin A (7-57); C506153:chromogranin A, rat; C121986:vasostatin; D001030:Apamin; D009569:Nitric Oxide; D013779:Tetrodotoxin; D019331:NG-Nitroarginine Methyl Ester