Effects of FK506 on exocrine pancreas in rats.
The efficacy of FK506 on exocrine pancreas was studied in rats. Male Sprague-Dawley rats (230-250 g) received an i.m. daily injection of FK506 (0.1, 0.5, or 5.0 mg/kg), cyclosporine (CS; 25 mg/kg), or saline for 2 weeks. Isolated dispersed pancreatic acini were prepared from rats, and enzyme content of the cells and secretory response to cholecystokinin (CCK) were determined. Amylase and trypsin contents were increased in a dose-related manner by FK506 (p less than 0.01) and by CS at 25 mg/kg (p less than 0.01). The release of amylase in response to CCK was reduced by FK506 in a dose-related manner (p less than 0.01) and by CS at 25 mg/kg (p less than 0.01). Histologic examination showed that treatment of rats with FK506 at 0.1 mg/kg did not affect morphology of the acinar cells. FK506 at 0.5 mg/kg induced a minimal number of small vacuoles in cytoplasm of acinar cells and FK506 at 5.0 mg/kg, and CS at 25 mg/kg induced numerous cytoplasmic vacuoles and pyknotic nuclei. Increased enzyme storage and suppressed responsiveness of amylase release may have an association with the histologic changes. Therefore, the results of this study suggest that FK506, even when used in a low dose, may have adverse effects on the exocrine pancreas. Understanding of the mechanism of action of FK506 on pancreas will provide essential basic information that will allow transplant practitioners to more fully explore the benefits of this drug.
Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock 72205.
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Doi
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Tangoku
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Inoue
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Chowdhury
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Rayford
D000681:Amylases / Q000378:metabolism; D000818:Animals; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D016559:Tacrolimus / Q000633:toxicity*
D000681:Amylases; D016559:Tacrolimus