tetragastrin and Chronic-Disease

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.

Topics: Animals; Azaserine; Cholecystokinin; Chronic Disease; Male; Organ Size; Pancreas; Pancreatic Neoplasms; Pancreatitis; Peptide Fragments; Precancerous Conditions; Rats; Rats, Inbred Lew; Receptors, Cholecystokinin; Sincalide; Tetragastrin