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.