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SUMMARY The roles of extracellular and intracellular mechanisms in the degradation of brush border proteins have been investigated by studying the small intestinal mucosa of dogs with naturally occurring exocrine pancreatic insufficiency. Peroral jejunal biopsies were homogenised and the organelles separated by isopycnic centrifugation on continuous sucrose density gradients. The distributions of marker enzymes for the principal subcellular organelles were determined in the gradients and related to the specific activities in the homogenates. There were increased activities of the brush border carbohydrases zinc-resistant x-glucosidase, maltase and sucrase in the pancreatic insufficient animals, but no change in lactase activity. The activity of y-glutamyl transferase was also higher in the affected group; the activities of two other brush border enzymes, alkaline phosphatase and leucyl-3-naphthylamidase, however, were unaltered. These findings with an increase in the modal density of the brush border from 1 20 to 1'22 are consistent with an enhanced glycoprotein content of the microvillus membrane. There were also rises in the activities of lysosomal enzymes. N-Acetyl-3-glucosaminidase activity was increased in the soluble fractions and the percentage latent enzyme activity was reduced, findings indicative of an increased fragility of the lysosomal membrane. There were no marked alterations in the activities or density gradient distributions of marker enzymes for the other organelles, stressing the specificity of the changes in the brush borders and lysosomes. These findings are compatible with the degradation of certain exposed brush border proteins by pancreatic proteases and suggest that when this is defective, intracellular degradative mechanisms may be stimulated.The enterocyte is a highly specialised cell involved in the terminal processing of nutrients and their transference from the lumen of the small intestine. Although the life span of this cell is relatively short, the protein content of the enterocyte is not static, proteins turning over at heterogeneous rates by a continuous process of synthesis and degradation (Alpers and Kinzie, 1973). A balance between these processes maintains the steady state level of individual proteins. Free ribosomes are responsible for the synthesis of intracellular proteins, whereas those destined for export or insertion into membranes are synthesised on the rough endoplasmic reticulum (Dallner et al., 1966).

COLITIS denotes inflammatory bowel disease affecting the large bowel, including the rectum. It accounts for about a third of all cases of chronic diarrhoea in the dog and presents with a number of diagnostically valuable clinical features. Inflammatory bowel disease can also affect the small intestine and both regions may be involved concurrently, resulting in a mixture of signs.

A new approach to the diagnosis of exocrine pancreatic insufficiency in the dog has been evaluated. The synthetic peptide, N-benzoyl-L-tyrosyl-paminobenzoic acid, administered orally, is specifically cleaved by pancreatic chymotrypsin to release p-aminobenzoic acid (PABA) which is subsequently absorbed and excreted in the urine. The assay of plasma PABA or the estimation of urinary excretion over a 6-hour period was found to give a clear differentiation between two small groups of healthy dogs and animals with pancreatic insufficiency. The absorption of orally administered sodium PABA was similar in the two groups confirming that the rate limiting process following oral peptide is hydrolysis not absorption.

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