Effect of Milk on Somatostatin Degradation in Suckling Rat Jejunum In Vivo

Abstract

Background:Somatostatin‐14 is present in breast milk, and intact somatostatin‐14 has been recovered from gastric lumen of infants. Studies have shown that somatostatin‐14 is metabolized in the intestinal luminal contents in vitro, which could be prevented by the presence of breast milk. In this study, the effect of milk on stability of somatostatin‐14 in suckling rat jejunum in vivo was examined.Methods:125I‐Somatostatin‐14[Tyr 11] was administered to the isolated jejunal loops in anesthetized suckling rats in the absence or presence of milk, fractions of milk, or known protease‐peptidase inhibitors. Structural integrity of 125I‐somatostatin‐14[Tyr 11] recovered from tissues at different intervals was analyzed by gel filtration and high‐performance liquid chromatography.Results:Radioactivity rapidly disappeared from the jejunal lumen with a 50% clearance achieved by 1.2 minutes. Gel filtration and high‐performance liquid chromatography analyses showed that 125I‐somatostatin‐14[Tyr 11] was rapidly degraded into smaller fragments. At 1 minute, jejunal luminal radioactivity was eluted in a major peak with retention time of 42.4 minutes, along with other minor peaks (retention time, 5.6, 8.0, 10.4, and 14.4 minutes); only a trace amount of intact 125I‐somatostatin‐14[Tyr 11] (retention time, 44.8 minutes) was present. Coadministration of rat's milk or its soluble fraction increased the level of intact 125I‐somatostatin‐14[Tyr 11] in the jejunal lumen and jejunal tissue. Presence of rat's milk‐casein or peptidase inhibitors (bestatin, phosphoramidon, or Bowman‐Birk inhibitor), however, failed to increase the level of intact 125I‐somatostatin‐15[Tyr 11].Conclusion:These results suggest that somatostatin‐14 is rapidly degraded in the jejunal lumen of suckling rats, and that milk‐borne peptidase inhibitors prevent this somatostatin‐14 degradation.