Structural and functional changes of exocrine pancreas induced by FK506 in rats.
BACKGROUND
The pancreas has been reported as a possible target for FK506 toxicity. This study was conducted to examine the effects of FK506 on the structure and function of pancreatic acinar cells.


METHODS
Male Sprague-Dawley rats received an intramuscular injection of saline or FK506, and pancreatic acini were isolated on the day of sacrifice.


RESULTS
FK506 caused a time-dependent suppression in amylase secretory response to cholecystokinin or carbachol at days 3-14, and increases in amylase and trypsinogen content at days 7-14. The properties of cholecystokinin and scopolamine binding sites in acini were not altered by FK506. Amylase release by A23187 and secretin were decreased by FK506, but those by phorbol ester 12-O-tetradecanoylphorbol-13-acetate, forskolin, 5'-cyclic adenosine monophosphate and vasoactive intestinal peptide were not changed. Increases in cytosolic free calcium concentration induced by cholecystokinin were not changed by FK506. Histologically, a significant increase in cytoplasmic zymogen granules was observed in pancreas from FK506-treated rats.


CONCLUSIONS
These data suggest that FK506 induced changes in function and metabolism in pancreatic acinar cells, and these changes might be caused by altering postreceptor loci in stimulus-secretion coupling.
Doi
R
R
Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock.
Inoue
K
K
Chowdhury
P
P
Kaji
H
H
Rayford
P L
PL
D000681:Amylases / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D002766:Cholecystokinin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005247:Feeding Behavior / Q000187:drug effects; D007700:Kinetics; D008297:Male; D019832:N-Methylscopolamine; D010179:Pancreas / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011949:Receptors, Cholecystokinin / Q000378:metabolism; D012016:Reference Values; D012601:Scopolamine / Q000494:pharmacology; D012602:Scopolamine Derivatives / Q000378:metabolism; D012633:Secretin / Q000494:pharmacology; D012844:Sincalide / Q000378:metabolism / Q000494:pharmacology; D016559:Tacrolimus / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D014362:Trypsinogen / Q000378:metabolism*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D011949:Receptors, Cholecystokinin; D012602:Scopolamine Derivatives; D012633:Secretin; D005576:Colforsin; D014660:Vasoactive Intestinal Peptide; D000001:Calcimycin; D001285:Atropine; D002217:Carbachol; D014362:Trypsinogen; D002766:Cholecystokinin; D012601:Scopolamine; D000681:Amylases; D012844:Sincalide; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D019832:N-Methylscopolamine; D016559:Tacrolimus