Ohlsson B, Borg K, Rehfeld J F, Ihse I, Axelson J
Department of Surgery, University Hospital, Lund, Sweden.
Int J Pancreatol. 1998 Dec;24(3):211-8. doi: 10.1007/BF02788424.
Intermittent injections of sulfated cholecystokinin-8 (CCK-8S) or devazepide caused long-lasting effects on cell proliferation in exocrine pancreas in contrast to continuous infusion. The acinar cells responded to both treatments with changes in the labeling index (LI) during the whole study period. When studying the influence of stimulation and inhibition of the CCK-A receptor on cell proliferation in the exocrine pancreas, not only are the drugs and doses of importance but also the mode of administration.
Continuous infusion of CCK-8S or the CCK-A receptor antagonist devazepide induces transient changes in acinar cell proliferation in rat pancreas. The aim of the present experiments was to study whether intermittent administration of CCK-8S or devazepide prevents receptor desensitization and thereby affects exocrine pancreatic cell proliferation persistently.
Male Sprague-Dawley rats were injected subcutaneously twice daily with CCK-8S (6 micrograms), devazepide (240 micrograms) or bovine serum albumin (BSA). The rats were sacrificed after 18 and 36 h and 3 and 7 d. One hour before sacrifice, the rats were injected intraperitoneally with 1 mCi/kg of tritiated thymidine. The pancreatic weight and the contents of water, protein, and DNA were determined. The LI (number of labeled cells/100 cells) of exocrine pancreatic cells was determined microscopically after autoradiography.
The concentration of plasma CCK was slightly increased by devazepide, but the increase was more pronounced by CCK-8S. The pancreatic wet weight was transiently increased 18 h after the start of CCK-8S injections (+14%), whereas devazepide caused a reduction after 7 d (-22%). The protein content was uninfluenced and the DNA content was decreased at 36 h with either treatment. CCK-8S increased the LI in acinar and centroacinar cells throughout the study period, but the ductal cell LI was increased only after 18 and 36 h. Injection of devazepide was followed by decreased LI of acinar cells throughout the study period. Also, the centroacinar and ductal cell LI decreased initially but returned to control values after 7 d.
与持续输注相比，间歇性注射硫酸化胆囊收缩素 -8（CCK-8S）或地伐西匹对胰腺外分泌部的细胞增殖产生持久影响。在整个研究期间，腺泡细胞对两种处理的反应均表现为标记指数（LI）的变化。在研究CCK-A受体的刺激和抑制对外分泌胰腺细胞增殖的影响时，不仅药物和剂量很重要，给药方式也很重要。
持续输注CCK-8S或CCK-A受体拮抗剂地伐西匹会引起大鼠胰腺腺泡细胞增殖的短暂变化。本实验的目的是研究间歇性给予CCK-8S或地伐西匹是否能防止受体脱敏，从而持续影响外分泌胰腺细胞增殖。
将雄性Sprague-Dawley大鼠每天皮下注射两次CCK-8S（6微克）、地伐西匹（240微克）或牛血清白蛋白（BSA）。在18小时、36小时、3天和7天后处死大鼠。在处死前1小时，给大鼠腹腔注射1毫居里/千克的氚标记胸腺嘧啶核苷。测定胰腺重量以及水、蛋白质和DNA的含量。放射自显影后，显微镜下测定外分泌胰腺细胞的LI（标记细胞数/100个细胞）。
地伐西匹使血浆CCK浓度略有升高，但CCK-8S引起的升高更为明显。CCK-8S注射开始后18小时，胰腺湿重短暂增加（+14%），而地伐西匹在7天后导致胰腺湿重降低（-22%）。两种处理对蛋白质含量均无影响，在36小时时DNA含量均降低。在整个研究期间，CCK-8S使腺泡细胞和中央腺泡细胞的LI增加，但导管细胞LI仅在18小时和36小时后增加。注射地伐西匹后，在整个研究期间腺泡细胞的LI降低。此外，中央腺泡细胞和导管细胞的LI最初降低，但在7天后恢复到对照值。
