Povoski S P, Zhou W, Longnecker D S, Roebuck B D, Bell R H
Department of Surgery, University of Cincinnati College of Medicine, Ohio 45267.
Cancer Res. 1993 Sep 1;53(17):3925-9.
Cholecystokinin (CCK) has been shown to stimulate the growth of both normal pancreas and azaserine-induced putative preneoplastic pancreatic lesions in the rat. The present study was performed to determine whether these effects are mediated by way of CCK-A receptors, CCK-B receptors, or both. Sixteen-day-old male Lewis rats were given i.p. injections of azaserine at 30 mg/kg body weight. Starting on day 21, rats were given s.c. injections, 5 days/week for 16 consecutive weeks, of either (a) CCK octapeptide (nonselective CCK agonist) (2.50 micrograms/kg body weight, n = 17), (b) tert-butyloxycarbonyl-Trp-Lys(epsilon-N-2-methylphenylaminocarbonyl++ +)-Asp- (N-methyl)-Phe-NH2 (highly selective CCK-A agonist) (1.84 micrograms/kg body weight, n = 18), (c) [(2R,3S)-beta-MePhe28,N-MeNle31]CCK26-33 (highly selective CCK-B agonist) (2.40 micrograms/kg body weight, n = 18), or (d) normal saline solution (control, n = 17). Rats were subsequently sacrificed, pancreatic weights were determined, and quantitative morphometric analysis of atypical acinar cell foci and nodules was performed. Both CCK octapeptide and the selective CCK-A agonist tert-butyloxycarbonyl-Trp-Lys(epsilon-N-2- methylphenylaminocarbonyl)-Asp-(N-methyl)-Phe-NH2 stimulated pancreatic growth and the development of acidophilic atypical acinar cell foci and nodules. Furthermore, the effect produced by the selective CCK-A agonist tert-butyloxycarbonyl-Trp-Lys(epsilon-N-2- methylphenylaminocarbonyl)-Asp-(N-methyl)-Phe-NH2 was greater than that produced by CCK octapeptide. In contrast, the selective CCK-B agonist [(2R,3S)-beta-MePhe28,N-MeNle31]CCK26-33 had no effect. These findings suggest that the growth of putative preneoplastic lesions (acidophilic atypical acinar cell foci and nodules) in the rat pancreas during the early stages of azaserine-induced pancreatic carcinogenesis is mediated specifically by way of CCK-A receptors.
胆囊收缩素（CCK）已被证明可刺激大鼠正常胰腺以及氮杂丝氨酸诱导的假定胰腺肿瘤前病变的生长。本研究旨在确定这些作用是通过CCK - A受体、CCK - B受体还是两者介导的。给16日龄雄性Lewis大鼠腹腔注射30mg/kg体重的氮杂丝氨酸。从第21天开始，大鼠皮下注射，每周5天，连续16周，分别注射：（a）CCK八肽（非选择性CCK激动剂）（2.50μg/kg体重，n = 17），（b）叔丁氧羰基 - Trp - Lys（ε - N - 2 - 甲基苯基氨基羰基） - Asp - （N - 甲基） - Phe - NH₂（高选择性CCK - A激动剂）（1.84μg/kg体重，n = 18），（c）[（2R，3S） - β - MePhe28，N - MeNle31]CCK26 - 33（高选择性CCK - B激动剂）（2.40μg/kg体重，n = 18），或（d）生理盐水溶液（对照组，n = 17）。随后处死大鼠，测定胰腺重量，并对非典型腺泡细胞灶和结节进行定量形态分析。CCK八肽和选择性CCK - A激动剂叔丁氧羰基 - Trp - Lys（ε - N - 2 - 甲基苯基氨基羰基） - Asp - （N - 甲基） - Phe - NH₂均刺激胰腺生长以及嗜酸性非典型腺泡细胞灶和结节的形成。此外，选择性CCK - A激动剂叔丁氧羰基 - Trp - Lys（ε - N - 2 - 甲基苯基氨基羰基） - Asp - （N - 甲基） - Phe - NH₂产生的作用大于CCK八肽产生的作用。相比之下，选择性CCK - B激动剂[（2R，3S） - β - MePhe28，N - MeNle31]CCK26 - 33没有作用。这些发现表明，在氮杂丝氨酸诱导的胰腺癌发生早期，大鼠胰腺中假定的肿瘤前病变（嗜酸性非典型腺泡细胞灶和结节）的生长是通过CCK - A受体特异性介导的。
