Effect of acetic acid or trypsin application on rat colonic motility in vitro and modulation by two synthetic fragments of chromogranin A.
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.
Ghia
Jean-Eric
JE
INSERM U575, Hôpital Civil Pavillon Poincaré, 67091 Strasbourg, France.
Jean-Eric
Ghia
G
Pradaud
Isabelle
I
Isabelle
Pradaud
P
Crenner
Francis
F
Francis
Crenner
C
Metz-Boutigue
Marie-Hélène
MH
Marie-Hélène
Metz-Boutigue
MB
Aunis
Dominique
D
Dominique
Aunis
A
Angel
Fabielle
F
Fabielle
Angel
A
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*
D053379:Chromogranin A; D002864:Chromogranins; D010446:Peptide Fragments; C437333:chromofungin; C489882:chromogranin A (4-16); D014357:Trypsin; D019342:Acetic Acid