Zucker K A, Adrian T E, Bilchik A J, Modlin I M
Department of Surgery, Yale University School of Medicine.
Am J Physiol. 1989 Oct;257(4 Pt 1):G511-6. doi: 10.1152/ajpgi.1989.257.4.G511.
Although exogenous administration of cholecystokinin (CCK) or dietary manipulation to increase circulating CCK have previously been shown to promote pancreatic growth, the role of CCK in controlling normal pancreatic development remains unclear. A potent CCK receptor antagonist, L364,718, was administered to rats, guinea pigs, and hamsters to block the effect of endogenous CCK. Animals were given continuous infusions of L364,718 (25 nmol.kg-1.h-1), CCK octapeptide [(CCK-8) 200 pmol.kg-1.h-1], or both CCK-8 and L364,718 for 14 and 28 days. Adult (4-mo-old) and young (4-wk-old) animals were used. CCK-8 and L364,718 were administered via separate, subcutaneously implanted mini-osmotic pumps. Infusions of CCK-8 alone for 28 days resulted in a 21.7% increase in wet pancreatic weight in 4-wk-old rats and a 22.7% increase in 4-wk-old guinea pigs (both P less than 0.001 compared with controls). Similar increases were found in DNA, RNA, and total protein contents. Coadministration of L364,718 totally blocked the trophic effects of exogenously infused CCK-8 in rats and guinea pigs. Administration of L364,718 alone in hamsters, guinea pigs, and rats for 14 and 28 days failed to alter the normal growth of the pancreas gland as measured by these parameters. Although elevated levels of CCK appear to promote a potent trophic response in the growing pancreas, this regulatory peptide does not appear to be an essential trophic factor for the normal growth of the exocrine pancreas in these animals.
尽管先前已表明，外源性给予胆囊收缩素（CCK）或通过饮食调控来增加循环中的CCK可促进胰腺生长，但CCK在控制正常胰腺发育中的作用仍不清楚。给大鼠、豚鼠和仓鼠注射一种强效CCK受体拮抗剂L364,718，以阻断内源性CCK的作用。给动物连续输注L364,718（25 nmol·kg⁻¹·h⁻¹）、CCK八肽[（CCK - 8）200 pmol·kg⁻¹·h⁻¹]，或同时输注CCK - 8和L364,718，持续14天和28天。使用成年（4月龄）和幼年（4周龄）动物。CCK - 8和L364,718通过单独皮下植入的微型渗透泵给药。单独输注CCK - 8 28天导致4周龄大鼠胰腺湿重增加21.7%，4周龄豚鼠增加22.7%（与对照组相比，两者P均小于0.001）。在DNA、RNA和总蛋白含量方面也发现了类似的增加。同时给予L364,718完全阻断了外源性输注的CCK - 8对大鼠和豚鼠的促生长作用。在仓鼠豚鼠和大鼠中单独给予L364,718 14天和28天，根据这些参数测量，未能改变胰腺的正常生长。尽管CCK水平升高似乎能促进生长中的胰腺产生强烈的促生长反应，但这种调节肽似乎不是这些动物外分泌胰腺正常生长所必需的促生长因子。
