title: A role for chromogranin A (4-16), a vasostatin-derived peptide, on human colonic motility. An in vitro study.
abstract: The hypothesis that CgA-derived peptides may be involved in mechanisms modulating motility was tested. Human colonic smooth muscles were studied using an organ bath technique. Acetic acid (AA) effects were characterized on spontaneous mechanical activities (SMA) and on responses to transmural nerve stimulation (NS). AA induced a significant decrease in tone and abolished SMA; this effect was insensitive to either TTX or L-NAME/apamin. The AA-induced inhibitory effects were significantly reduced in the presence of CgA4-16. This effect was insensitive to TTX or L-NAME/apamin. Furthermore, AA-induced effects were blocked in the presence of BAYK8644 and CgA4-16 together. The inhibitory effect of nifedipine was delayed in the presence of CgA4-16. NS induced a triphasic response. Only the excitatory components were reduced in the presence of AA. This effect was dose-related and remained unchanged in the presence of CgA4-16 alone, but was blocked in the presence of simultaneous administration of CgA4-16 and L-NAME/apamin. AA application induced inhibition of human colon motility in vitro. This effect may be mediated through an action on L-type calcium channels. CgA4-16 may display a protective role, which prevents the inhibition of motility due to AA to occur, by acting on both smooth muscle and afferent terminals.
authors.affiliation: INSERM Unit 575 Pavillon Poincaré 1 place de l'Hôpital Civil 67091 Strasbourg, France.
authors.forename: Jean-Eric
authors.initials: JE
authors.lastname: Ghia
authors.forename: Francis
authors.initials: F
authors.lastname: Crenner
authors.forename: Serge
authors.initials: S
authors.lastname: Rohr
authors.forename: Christian
authors.initials: C
authors.lastname: Meyer
authors.forename: Marie-Helene
authors.initials: MH
authors.lastname: Metz-Boutigue
authors.forename: Dominique
authors.initials: D
authors.lastname: Aunis
authors.forename: Fabielle
authors.initials: F
authors.lastname: Angel
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D019342:Acetic Acid / Q000494:pharmacology; D001030:Apamin / Q000494:pharmacology; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D053379:Chromogranin A; D002864:Chromogranins / Q000138:chemical synthesis / Q000494:pharmacology*; D012809:Colon, Sigmoid / Q000166:cytology / Q000187:drug effects* / Q000294:innervation; D004558:Electric Stimulation; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006801:Humans; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects* / Q000294:innervation; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D009924:Organ Culture Techniques; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D053379:Chromogranin A; D002864:Chromogranins; D010446:Peptide Fragments; C489882:chromogranin A (4-16); D001030:Apamin; D013779:Tetrodotoxin; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009543:Nifedipine; D019342:Acetic Acid; D019331:NG-Nitroarginine Methyl Ester