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Am J Physiol Gastrointest Liver Physiol 246: G675-G682, 1984;
0193-1857/84 $5.00
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AJP - Gastrointestinal and Liver Physiology, Vol 246, Issue 6 675-G682, Copyright © 1984 by American Physiological Society

ARTICLES

Catabolism of neurotensin in interstitial fluid of the rat stomach

N. W. Bunnett, M. Mogard, M. S. Orloff, H. J. Corbet, J. R. Reeve Jr and J. H. Walsh

The catabolism of neurotensin (NT) was studied in the gastric submucosa of the conscious rat using a novel technique to obtain a dialysate of interstitial fluid. A microdialysis fiber system was surgically implanted into the gastric submucosa, and 2 days later experiments were commenced on conscious animals. Isotope-labeled NT was administered to the tissue, and a dialysate of the submucosal interstitial fluid was collected. In the dialysate, NT and catabolites of NT formed in the interstitial fluid were identified and quantitated by high-pressure liquid chromatography. The catabolism of 125I-NT-(1-13) and [3H]NT-(1-13) was studied as was the further breakdown of the major catabolites. NT-(1-13) was, regardless of the type of label, catabolized mainly into NT-(1-8), NT-(9-13), NT-(1-11), and free tyrosine. None of the catabolites formed is known to possess significant biological activity. NT-(9-13) was rapidly cleared, whereas the amino-terminal fragments NT-(1-8) and NT-(1-11) were more resistant to degradation. The biological half-life of neurotensin in the gastric submucosa of the rat was between 9 and 15 min.


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