The Effects of Prednisolone on the Rat Enterocyte at a Subcellular Level

Batt, R. M.; Wells, G.

doi:10.1042/cs0550435

Cited by 4 publications

(2 citation statements)

References 12 publications

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“…This was also true for particulate tris-resistant oc-glucosidase activity, suggesting that there was no major change in the endoplasmic reticulum and being consistent with the hypothesis that a decreased rate of degradation is responsible for the increased activities of specific brush border enzymes. This is in contrast with the increased activities in the prednisolone-treated animal, where a proliferation of the rough endoplasmic reticulum suggests an enhanced rate of synthesis of brush border enzymes and carrier proteins Batt et al, 1978).…”

Section: Discussionmentioning

confidence: 59%

Biochemical changes in the jejunal mucosa of dogs with naturally occurring exocrine pancreatic insufficiency

Batt¹,

Bush²

1979

Gut

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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).

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Section: Discussionmentioning

confidence: 59%

Biochemical changes in the jejunal mucosa of dogs with naturally occurring exocrine pancreatic insufficiency

Batt¹,

Bush²

1979

Gut

Self Cite

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“…This view is additionally supported by the relationship between brush border enzyme activity and epithelial cell RNA-that is, brush border enzyme activity: RNA contentwhich was similar in the three groups. Furthermore, in the rat intestine prednisolone significantly increases RNA associated with the rough endoplasmic reticulum-that is, membrane bound ribosomes and associated RNA-and significantly increases 14Ctryosine labelling of brush border proteins (Scott et al, 1977;Batt et al, 1978). It therefore appears likely that prednisolone is inducing the synthesis of brush border enzymes and transporters and could be acting by harnessing an underlying physiological mechanism.…”

Section: Discussionmentioning

confidence: 99%

Enhancement of ileal adaptation by prednisolone after proximal small bowel resection in the rat.

Scott¹,

Batt²

1979

Gut

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SUMMARY The effect of prednisolone on the adapted ileum of the rat after jejunal resection was examined. Three weeks after 50 % proximal small bowel resection animals were fed pharmacological doses of soluble prednisolone (0.75 mg/kg/day) over a one week period, and killed at four weeks. Animals treated with prednisolone showed significant increases in brush border oc-glucosidase, leucyl-2-napththylamidase and y-glutamyl transferase (p < 0.01) per unit length of intestine compared with resection alone and transection reanastomosis control groups. This increase was the result of a significant enhancement (p < 0.01) of brush border digestive enzyme activity per milligram of epithelial cell DNA-that is, per enterocyte-and was associated with a similar increase in enterocyte RNA content. In contrast, the activities of lysosomal and mitochondrial marker enzymes per milligram of DNA were similar in each group. Cell proliferation was not further stimulated by prednisolone. Thus prednisolone can selectively enhance brush border digestive capacity after intestinal resection without increasing cell proliferation. The increase in enterocyte RNA suggests that enzyme induction may be the mechanism of this effect.In a number of species, including man, after partial resection of the small bowel the remaining small intestine undergoes an adaptive response (Booth et al., 1959;Porus, 1965;Dowling and Booth, 1967;Weinstein et al., 1969;Weser and Hernandez, 1971

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Intestinal adaptation in short-bowel syndrome

Lentze

1989

Eur J Pediatr

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After massive resection of the small intestine the remnant mucosa has an important capacity to enlarge the absorptive surface for the digestion, hydrolysis and absorption of nutrients. This intestinal adaptation is achieved by the interaction of various factors. Oral nutrients together with pancreatic biliary secretions stimulate the mucosa to become hyperplastic. Secondary to these luminal factors hormones play an important role in the adaptive process. Among the hormones, enteroglucagon is the most important growth promoting agent together with other growth factors such as epidermal growth factor, prostaglandin E2 and human growth hormone analogues, e.g. plerocercoid growth factor from the plerocercoid larvae of the tapeworm Spirometra mansonoides. The intestinal enterocyte is the target of these factors and within the cell the synthesis of polyamines, which are responsible for rapid growth, is the most essential step for the development of hyperplasia after resection. The rate limiting enzyme for polyamine synthesis ornithine decarboxylase (ODC) reacts to trophic stimuli with an increased activity. Thereafter rapid accumulation of tissue polyamines occurs. Blockade of ODC by specific inhibitors is accompanied by absence of intestinal hyperplasia after resection. Therefore it is concluded that ODC plays a key role in the intestinal adaptation of the remnant small bowel. To start and enhance intestinal hyperplasia after resection in patients with short bowel syndrome introduction of oral nutrition as soon as possible after operation is very important. On account of gastric acid hypersecretion the use of H2 receptor blocking agents is recommended. A decreased intestinal transit time is treated with loperamide.(ABSTRACT TRUNCATED AT 250 WORDS)

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The Effects of Prednisolone on the Rat Enterocyte at a Subcellular Level

Cited by 4 publications

References 12 publications

Biochemical changes in the jejunal mucosa of dogs with naturally occurring exocrine pancreatic insufficiency

Biochemical changes in the jejunal mucosa of dogs with naturally occurring exocrine pancreatic insufficiency

Enhancement of ileal adaptation by prednisolone after proximal small bowel resection in the rat.

Intestinal adaptation in short-bowel syndrome

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