Stimulation of Cl〔-〕 Secretion by L-Alanine Oligopeptides in the Mammalian Large Intestine

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  • Stimulation of Cl- Secretion by L-Alanine Oligopeptides in the Mammalian Large Intestine.

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A variety of oligopeptides are probably released within the intestinal tissue under inflammatory conditions or during peptide absorption. To examine whether some of these peptides can affect intestinal transport functions, we determined the effects of l-alanine oligopeptide on short-circuit current (Isc) and transmucosal conductance (Gt) in submucosa-mucosa preparations from the mouse cecum and guinea pig distal colon in vitro in Ussing chambers. l-Alanyl-l-alanine (Ala-Ala, 10 mm) added to the serosal side increased Isc and Gt, giving a peak followed by a sustained phase (the peak increase in Isc was 45 ± 6 μA/cm2 and the increase in Gt was 0.55 ± 0.11 mS/cm2). The tripeptide, l-alanyl-l-alanyl-l-alanine (Ala-Ala-Ala, 10 mm), added to the serosal side also induced increases in Isc and Gt by a similar degree. On the other hand, luminal Ala-Ala, and serosal l-alanine and d-alanine (10 mm) caused significantly smaller increases in Isc and Gt (~15 μA/cm2 and ~0.15 mS/cm2, respectively). The Ala-Ala induced increase in Isc was partially inhibited by serosal bumetanide (0.1 mm) and mucosal 5-nitro-2-(3-phenylpropylamino)benzoic acid (0.1 mm), and largely suppressed by removing Cl− from the bathing solution. The increase in Isc was largely suppressed by serosal low Ca2+ and tetrodotoxin, but was not affected by indomethacin. In the guinea pig distal colon, serosal Ala-Ala (10 mm) evoked a transient increase in Isc by 23 ± 7 μA/cm2 and an increase in Gt by 1.2 ± 0.3 mS/cm2. These results suggest that Ala-Ala, and probably also Ala-Ala-Ala, added to the serosal side stimulated electrogenic Cl− secretion mainly through the activation of submucosal secretomotor neurons in the mammalian large intestine. <br>

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