Effect of milk on somatostatin degradation in suckling rat jejunum in vivo.
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-14[Tyr 11].


CONCLUSIONS
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.
Rao
R K
RK
Department of Pharmacology, University of Arizona Health Sciences Center, Tucson, USA.
Davis
T P
TP
Williams
C
C
Koldovsky
O
O
D000818:Animals; D000833:Animals, Suckling; D002851:Chromatography, High Pressure Liquid; D005260:Female; D007457:Iodine Radioisotopes; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008892:Milk; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013004:Somatostatin / Q000378:metabolism*
D007457:Iodine Radioisotopes; D011480:Protease Inhibitors; D013004:Somatostatin