Camp. Biochem. Physiol. Vol. 87A, No. 3, pp. 657-663, 1987 0300- 9629/87 $3.00 + 0.00 Printed in Great Britain 0 1987 Pergamon Journals Ltd INTESTINAL RELEASE OF MUCIN IN RESPONSE TO HCl AND TAUROCHOLATE: EFFECT OF INDOMETHACIN B. L. SLOMIANY, M. KOSMALA, S. R. CARTER,S. J. KONTUREK, J. BILSKI and A. SLOMIANY Gastroenterology Research Laboratory, Department of Medicine, New York Medical College, Valhalla, New York 10595, USA (Received 8 September 1986) Abstract-l. Alkaline secretion and mucin output were analyzed along the gastrointestinal tract of a dog in response to luminal application of HCl and taurocholate with and without pretreatment with indomethacin. 2. Mucins derived from the different areas displayed similar contents of protein and carbohydrate but differed with respect to associated and covalently bound lipids. 3. Application of HCl or taurocholate in all the regions caused an increase in the output of mucins and HCO;. However, mucins elaborated in response to HCl exhibited higher total lipid content and were richer in phospholipids. 4. Pretreatment with indomethacin prior to HCl application led to a reduction in HCO; and caused a decrease in mucin phospholipid content, but had no effect on HCO; secretion and the lipid content of mucins elaborated in response to taurocholate. 5. The results indicate that mucins elaborated along the gastrointestinal tract differ with respect to lipids, and that their output in response to HCl is mediated by prostaglandins. INTRODUCTION The resilient layer of mucus which tenaciously ad- heres to the epithelial surfaces of the alimentary tract constitutes the first line of mucosal defense against various exogenous and endogenous insults. In the oral cavity, this layer not only provides protection to soft tissue but also plays a role in the defense of teeth against abrasion and caries (Tabak et al., 1982; Slomiany et al., 1986). In the gastrointestinal tract, mucus is an integral part of a barrier which protects the underlying mucosa from injury by luminal con- tents and microbial insults (Allen, 1981; Beachy, 1981; Slomiany er al., 1985). The constituents of mucus represent a heterogeneous mixture of mole- cules which find their way to the mucosal surface either by a process of active secretion or by passive transudation, and include proteins, glycoproteins and lipids. These molecules together with water and elec- trolytes form a dynamic continuum which assures a multitude of protective physicochemical and biologi- cal functions. Included among those are lubrication, permselectivity, regulation of peptic activity, control of bacterial proliferation, and provision of a milieu for the neutralization of the diffusing luminal acid by the HCO; secreted from the epithelial surfaces (Allen, 1981; Flemstrom and Garner, 1982; Murty et al., 1984; Sarosiek et al., 1984). The process of HCO; secretion in response to acid irritation appears to involve the prostaglandin mechanism and is affected by nonsteroidal antiinflammatory agents such as aspirin and indomethacin that inhibit cyclooxygenase enzyme activity (Johansson and Bergstrom, 1982; Miller, 1983). Increased output of HCO; also char- acterizes the mucosal response to such endogenous irritants as bile salts, but in this case the enrichment results from an increased permeability of the mucosa to HCO; rather than active secretion and is not affected by indomethacin (Miller, 1983; Konturek, 1985). Studies on the HCO; secretion along the gastro- intestinal tract indicate that its output varies de- pending on the region with the highest being in the duodenum (Swierczek and Konturek, 1981; Konturek et al., 1984; Flemstrom et al., 1985). Con- siderably less is known about the secretion of mucus in these regions and whether any qualitative differences exist between mucus elaborated by areas of gastrointestinal tract often exposed to acid and those that rarely come into contact with acid. Fur- thermore, nothing is known about compositional differences in mucus produced in response to acid and to the irritants such as bile salts, the action of which does not seem to involve prostaglandins. Earlier, the gastroduodenal alkaline response to acid and tauro- cholate was reported (Konturek et al., 1984). Here, data on the content and composition of mucins elaborated by dog intestinal mucosa exposed to HCI and taurocholate is presented. MATERIALS AND METHODS Animal preparation The studies were performed with 30 mongrel dogs (Cunis familiaris) of both sexes, weighing 15-24 kg. Ten animals were used for preparation of vagally denervated fundic and antral pouches, and ten for preparation of loops (7 cm long), fashioned from proximal and distal duodenum. In five dogs, the isolated loops were prepared from the upper portion of jejunum and in another five animals loops were fashioned 657