Effects of Malnutrition and Chronic Reserpine Treatment on Pancreatic Exocrine Function1

Hazlett, Dee Allen; Korc, Murray; Brannon, Patsy M.

doi:10.1203/00006450-198612000-00009

Cited by 9 publications

(11 citation statements)

References 14 publications

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“…In contrast, the decreased content of amylase, the increased content of chymotrypsinogen, and the diminution in body wt cannot specifically be attributed solely to reserpine because malnutrition alone could also induce similar effects in the group of pair-fed animals. The latter conclusions are similar to those of Hazlett et al (23) and Webster et al (24), who also observed that decreased levels of amylase and total proteins could be secondary to malnutrition. The increase observed in lipase content, however, was not observed by Hazlett et al (23).…”

Section: Discussionsupporting

confidence: 91%

Alterations of Pancreatic Growth and of GP-2 Content in the Reserpinized Rat Model of Cystic Fibrosis

1989

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ABSTRACT. The chronically reserpinized rat is an experimental model for cystic fibrosis. In this study, we report the effects of two doses of reserpine (0.5 and 1.0 m g kg-'. d-') on the growth of the pancreas and on its content of the glycoprotein GP-2, a characteristic protein of the zymogen granule. An assessment of the effects of secondary malnutrition induced by the drug was also performed by adding a group of pair-fed animals. During the 7 d of treatment, body wt and food intake were monitored. These two parameters were significantly affected from the 4th d on. Pancreatic wt, DNA, protein, and activity of amylase and chymotrypsinogen were measured after 4 and 7 d of treatment; lipase activity and GP-2 content, after 7 d. Although the DNA content never did change, total protein diminished by 27% at the higher dose of reserpine. Pancreatic wt, amylase activity and GP-2 content were reduced by the treatment, while chymotrypsinogen and lipase activities were increased. Effects on pancreatic wt, amylase, chymotrypsinogen, and GP-2 were dose-dependent. Malnutrition had effects similar to reserpine on body wt, protein, amylase, and chymotrypsinogen. Pancreatic wt, lipase, and GP-2, however, were specifically altered by the chronic reserpine treatment. It is concluded from these results that reserpine induces, in the pancreas, specific alterations that are distinguishable from the accompanying malnutrition. These findings support the use of pancreatic wt, lipase, and GP-2 as specific markers of the effects of the drug on the pancreatic tissue in the chronically reserpinized rat model for cystic fibrosis. This is the first report of a modulation of GP-2 content induced by any treatment. It suggests that GP-2 is directly affected in the pancreas of the chronically reserpinized rat. (Pediafr Res 25: [478][479][480][481]1989) Abbreviations CF, cystic fibrosis GP-2, the major pancreatic granule membrane glycoprotein R group, rats injected at 0.5 mg . kg-'. d-' with reserpine 2R group, rats injected at 1.0 mg . kg-'. d-' with reserpine CF is the most common genetic disease in the Caucasian population, occurring once in every 2000 live births. It is characterized by a generalized disorder of the exocrine glands. The

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Section: Discussionsupporting

confidence: 91%

Alterations of Pancreatic Growth and of GP-2 Content in the Reserpinized Rat Model of Cystic Fibrosis

1989

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“…This secretion was decreased in the R500, R5, and PFS rats. In a previous study, pancreatic acini from rats treated with 500 /Ig/kg reserpine secrete significantly less amylase in response to cholecystokinin than do acini from control rats, while acini from PFS rats show intermediate secretion between reserpine-treated and control acini (14). In the present study using M carbachol, amylase secretion by acini from PFS rats also tended to be intermediate between that of C and R500 or R5 acini.…”

supporting

confidence: 51%

“…Pancreatic protein and amylase activity are decreased similarly in chronically reserpine-treated and PFS rats (restricted to the food consumption of the chronically reserpinetreated rats), but pancreatic amylase secretion is significantly less in acini isolated from chronically reserpine-treated rats compared to acini from PFS rats. These results indicate that some effects of reserpine, but not all, may be due to the induced malnutrition (14).…”

mentioning

confidence: 74%

“…Chronic reserpine treatment also decreases food consumption (14,15) and growth in rats and mice (4,(13)(14)(15), resulting in malnutrition (14). Pancreatic protein and amylase activity are decreased similarly in chronically reserpine-treated and PFS rats (restricted to the food consumption of the chronically reserpinetreated rats), but pancreatic amylase secretion is significantly less in acini isolated from chronically reserpine-treated rats compared to acini from PFS rats.…”

mentioning

confidence: 99%

“…parameter not sharing a superscript are significantly different (p < 0.05) Pancreata were homogenized as described previously (14) in by ANOVA and LSD, phosphate-buffered saline and centrifuged at 16,000 x g, and 4°C for 30 min. An aliquot of the supernatant was removed for proteolytic analysis, and soybean trypsin inhibitor (final concen-8.1 Tris buffer containing 0.02 M Ca2' for maximal enzyme tration 0.1%) was added to the remaining supernatant.…”

mentioning

confidence: 99%

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Effects of Reserpine Treatment on Dietary Adaptation of the Rat Exocrine Pancreas

Hazlett

Brannon

1988

Pediatr Res

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ABSTRACT. Chronic reserpine treatment (500 pg/kg) of the rat results in generalized exocrinopathy, impaired pancreatic secretion, and decreased pancreatic amylase. These characteristics are similar to those in cystic fibrosis and are the basis for use of this experimental model for cystic fibrosis. Pancreatic enzymes adapt to diet, but it is not known whether chronic reserpine treatment affects this response. Due to the malnutrition induced by this treatment, another dose of reserpine was required that would alter pancreatic function but not induce malnutrition in order to evaluate dietary adaptation. Male rats (100-120 g) were injected subcutaneously daily for 7 days with 1) no injection (control); 2) 1.0 ml/kg vehicle or sham (pair fedsham); or 3) reserpine: 500,50, or 5 pglkg. Food consumption was comparable among control and reserpine-treated (50 and 5 pg/kg) rats and significantly greater (200%) than pair fed-sham and 500 pg/kg reserpine-treated rats. Pancreatic amylase, however, was significantly lower in all reserpine-treated rats (500 pg/kg, 74%; 50 pg/kg, 56%; 5 pglkg, 52%) than in control rats. To evaluate dietary adaptation, control and reserpine-treated (5 pg/kg) rats were fed high carbohydrate, high fat or high protein diets. Both groups adapted to these diets with the greatest amylase, lipase, and trypsin activities in high carbohydrate-, high fat-, and high protein-fed rats, respectively. Reserpine-treated rats fed high carbohydrate, however, had significantly lower (64%) amylase activity than high carbohydrate-fed control rats. Although reserpine-treated rats can adapt pancreatic enzymes to diet, the adaptation of amylase to carbohydrate is impaired. (Pediatr Res 23: 176-180,1988) Abbreviations PFS, pair-fed sham C, control R500, reserpine-treated with 500 pglkg R50, reserpine-treated with 50 pg/kg R5, reserpine-treated with 5 pg/kg HC, high carbohydrate HF, high fat HP, high protein ANOVA, analysis of variance LSD, least significant difference

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Plasma immunoreactive cationic trypsin(ogen) pattern in reserpinized rat model of cystic fibrosis

Weizman

1996

Digest Dis Sci

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Plasma immunoreactive cationic trypsin (ogen) is elevated in cystic fibrosis during early infancy, before exocrine pancreatic insufficiency is fully developed. The recently developed cystic fibrosis mouse model carrying a mutated gene presents only minor pathologic findings in the pancreas. However, the reserpinized rat model shows cystic fibrosis-like defects in various exocrine glands, including the exocrine pancreas. Plasma immunoreactive cationic trypsin (ogen) has not been studied yet in this model. The present study explored the plasma immunoreactive cationic trypsin (ogen) pattern and possible mechanisms in this rat model. Plasma immunoreactive cationic trypsin (ogen) (RIA), pancreatic juice volume, protein, and trypsin, and pancreas weight were determined in rats treated with reserpine (0.5 mg/kg/day subcutaneously) for four or seven days, following cerulein stimulation (5 micrograms/kg/dose intraperitoneally), versus pair-fed controls. The first of four consecutive 30 min periods revealed peak values in all parameters. Four-day reserpine-treated rats demonstrated significantly higher plasma immunoreactive cationic trypsin (ogen) levels (167.3 +/- 12.8 vs 88.9 +/- 6.1 ng/ml; P < 0.0001) with similar values of pancreatic juice trypsin (8.2 +/- 2.4 vs 6.6 +/- 1.8 units/mg protein; P = NS) and volume (5.6 +/- 1.3 vs 4.2 +/- 1.6 mg/min/g pancreas; P = NS), compared to controls. Rats treated with reserpine for seven days revealed significantly lower values of plasma immunoreactive cationic trypsin (ogen) (39.2 +/- 8.4 vs 66.8 +/- 4.9 ng/ml; P < 0.001), pancreatic juice trypsin (1.9 +/- 0.3 vs 3.2 +/- 0.9 units/mg protein; P < 0.001) and volume (1.6 +/- 0.7 vs 3.1 +/- 0.6 mg/min/g pancreas; P < 0.001) compared to controls. We conclude that the reserpinized rat model resembles human cystic fibrosis as to elevated plasma immunoreactive cationic trypsin (ogen) before exocrine pancreatic insufficiency is fully developed. Since exocrine pancreatic volume secretion is intact at this stage, the mechanism of elevated plasma immunoreactive cationic trypsin is probably not due to ductular obstruction. We suggest that this model be studied further in order to investigate other possible mechanisms.

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Effects of Malnutrition and Chronic Reserpine Treatment on Pancreatic Exocrine Function1

Cited by 9 publications

References 14 publications

Alterations of Pancreatic Growth and of GP-2 Content in the Reserpinized Rat Model of Cystic Fibrosis

Alterations of Pancreatic Growth and of GP-2 Content in the Reserpinized Rat Model of Cystic Fibrosis

Effects of Reserpine Treatment on Dietary Adaptation of the Rat Exocrine Pancreas

Plasma immunoreactive cationic trypsin(ogen) pattern in reserpinized rat model of cystic fibrosis

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