Doi R, Inoue K, Chowdhury P, Kaji H, Rayford P L
Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock.
Gastroenterology. 1993 Apr;104(4):1153-64. doi: 10.1016/0016-5085(93)90287-m.
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.
Male Sprague-Dawley rats received an intramuscular injection of saline or FK506, and pancreatic acini were isolated on the day of sacrifice.
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.
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.
已有报道称胰腺可能是FK506毒性的一个靶点。本研究旨在探讨FK506对胰腺腺泡细胞结构和功能的影响。
雄性Sprague-Dawley大鼠接受肌肉注射生理盐水或FK506，在处死当天分离胰腺腺泡。
在第3 - 14天，FK506导致对胆囊收缩素或卡巴胆碱的淀粉酶分泌反应呈时间依赖性抑制，在第7 - 14天淀粉酶和胰蛋白酶原含量增加。FK506未改变腺泡中胆囊收缩素和东莨菪碱结合位点的特性。FK506降低了A23187和促胰液素诱导的淀粉酶释放，但佛波酯12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯、福斯可林、5'-环磷酸腺苷和血管活性肠肽诱导的淀粉酶释放未改变。FK506未改变胆囊收缩素诱导的胞质游离钙浓度升高。组织学上，在接受FK506治疗的大鼠胰腺中观察到细胞质酶原颗粒显著增加。
这些数据表明FK506诱导了胰腺腺泡细胞功能和代谢的变化，这些变化可能是由刺激 - 分泌偶联中受体后位点的改变引起的。
