title: Effect of acetic acid or trypsin application on rat colonic motility in vitro and modulation by two synthetic fragments of chromogranin A.
abstract: The hypothesis that Chromogranin A (CgA)-derived peptides are involved in mechanisms modulating altered colonic motility was tested. Rat distal colonic strips were studied using an organ bath technique. Acetic acid (AA)-induced effects were characterized on spontaneous mechanical activities (SMA) in the presence of CgA4-16 or CgA47-66. In preparations with mucosa, AA induced a transient hyperactivity followed by a decrease in tone. The first phase is sensitive to tetrodotoxin (TTX) and capsaicin. The second phase was sensitive to BAYK8644 but insensitive to L-nitro-arginine-methyl-ester (L-Name)/apamin together. CgA4-16 or CgA47-66 alone produced no change on SMA. The administration of CgA4-16 prior to AA increased the duration of the excitatory component and reduced tone inhibition. CgA47-66 prior to AA only decreased duration of the excitatory phase. In preparations without mucosa, AA decreased tone. This effect was sensitive to BAYK8644 and CgA4-16. Trypsin decreased basal tone. This effect was suppressed by TTX, BAYK8644 or L-Name/apamin and were reduced by CgA4-16. AA-induced effects on rat colonic motility in vitro may be mediated through activation of primary afferents and an action at L-Type calcium channels. CgA-derived peptides are shown to decrease AA-induced effects on motility.
authors.affiliation: INSERM U575, Hôpital Civil Pavillon Poincaré, 67091 Strasbourg, France.
authors.forename: Jean-Eric
authors.initials: JE
authors.lastname: Ghia
authors.forename: Ghia
authors.initials: G
authors.lastname: Jean-Eric
authors.forename: Isabelle
authors.initials: I
authors.lastname: Pradaud
authors.forename: Pradaud
authors.initials: P
authors.lastname: Isabelle
authors.forename: Francis
authors.initials: F
authors.lastname: Crenner
authors.forename: Crenner
authors.initials: C
authors.lastname: Francis
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Metz-Boutigue
authors.forename: Metz-Boutigue
authors.initials: MB
authors.lastname: Marie-Hélène
authors.forename: Dominique
authors.initials: D
authors.lastname: Aunis
authors.forename: Aunis
authors.initials: A
authors.lastname: Dominique
authors.forename: Fabielle
authors.initials: F
authors.lastname: Angel
authors.forename: Angel
authors.initials: A
authors.lastname: Fabielle
mesh_terms: D019342:Acetic Acid / Q000494:pharmacology*; D000818:Animals; D053379:Chromogranin A; D002864:Chromogranins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D003106:Colon / Q000187:drug effects* / Q000502:physiology; D005769:Gastrointestinal Motility / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000502:physiology; D008297:Male; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014357:Trypsin / Q000494:pharmacology*
chemical_list: D053379:Chromogranin A; D002864:Chromogranins; D010446:Peptide Fragments; C437333:chromofungin; C489882:chromogranin A (4-16); D014357:Trypsin; D019342:Acetic Acid