Distribution and metabolism of intravenously administered trefoil factor 2/porcine spasmolytic polypeptide in the rat

Abstract

Background—Trefoil peptides are secreted by mucus producing cells in the gastrointestinal tract and are supposed to be involved in oligomerisation processes of the mucin glycoproteins in the lumen. Endocrine functions have also been suggested.Aims—To target possible binding sites for iodine-125 labelled porcine spasmolytic polypeptide (pSP) in an in vivo rat model.Methods—125I-pSP was given by intravenous injection to female Spraque-Dawley rats. The distribution of 125I-pSP was assessed by gamma counting of samples of organs and by autoradiography of paraffin wax embedded sections. The degradation of 125I-pSP was studied by trichloroacetic acid precipitation, and the saturability of binding by administration of excess unlabelled peptide.Results—125I-pSP was taken up in the kidneys and the gastrointestinal tract and was excreted almost unmetabolised in the urine. In the stomach, it could be displaced by unlabelled pSP in a dose dependent manner. Autoradiography showed grains in mucous neck cells, parietal cells, the mucus layer, and the pyloric glands of the stomach; in Brunner’s glands and the Paneth cells in the small intestine; and in cells in the lower part of the crypts in the colon.Conclusions—125I-pSP from the circulatory system is taken up by mucus producing cells in the gastrointestinal tract. The binding can be displaced by non-radioactive pSP, suggesting the presence of a receptor.