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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.

A novel stimulant of gastric acid secretion was extracted and purified from the non-antral gastric mucosa of the canine stomach and some of its biological properties were examined. Tissue was boiled in water and extracted in 2% trifluoroacetic acid. The stimulatory activity was purified by a combination of reverse-phase high pressure liquid chromatography (HPLC) and gel filtration. Fractions were assayed for a stimulation of basal, pentagastrin- and histamine-stimulated gastric acid secretion in the anaesthetized rat. Stimulatory activity was eluted from reverse-phase HPLC columns with acetonitrile and its elution from Sephadex G-10 and G-50 columns suggested a molecular weight of 1,000 to 3,000. The highly purified extracts enhanced basal, pentagastrin- and histamine-stimulated acid secretion in the rat. A stimulatory fraction was purified which was devoid of immunoreactive gastrin and gastrin-releasing peptide and contained only small amounts of histamine. Its chromatographic properties differed from those of histamine and acetylcholine. On two occasions the stimulant was purified to homogeneity and found to contain amino acids. Insufficient pure material was obtained for full characterization. The stimulant has been tentatively called oxyntin.