STIMULATION OF GROWTH OF AZASERINE-INDUCED PUTATIVE PRENEOPLASTIC LESIONS IN RAT PANCREAS IS MEDIATED SPECIFICALLY BY WAY OF CHOLECYSTOKININ-A RECEPTORS

Cholecystokinin (CCK) has been shown to stimulate the growth of both n ormal pancreas and azaserine-induced putative preneoplastic pancreatic lesions in the rat. The present study was performed to determine whet her These effects are mediated by way of CCK-A receptors, CCK-B recept ors, or both. Sixteen-day-old male Lewis rats were given i.p. injectio ns of azaserine at 30 mg/kg body weight. Starting on day 2 1, rats wer e given s.c. injections, 5 days/week for 16 consecutive weeks, of eith er (a) CCK octapeptide (nonselective CCK agonist) (2.50 mug/kg body we ight, n = 17), (b) -methylphenylaminocarbonyl)-Asp-(N-methyl)-Phe-NH2 (highly selective CCK-A agonist) (1.84 mug/kg body weight, n = 18), (c ) [(2R,3S)-beta-MePhe28,N-MeNle31]CCK26-33 (highly selective CCK-B ago nist) (2.40 mug/kg body weight, n = 18), or (d) normal saline solution (control, n = 17). Rats were subsequently sacrificed, pancreatic weig hts were determined, and quantitative morphometric analysis of atypica l acinar cell foci and nodules was performed. Both CCK octapeptide and the selective CCK-A agonist -methylphenylaminocarbonyl)-Asp-(N-methyl )-Phe-NH2 stimulated pancreatic growth and the development of acidophi lic atypical acinar cell foci and nodules. Furthermore, the effect pro duced by the selective CCK-A agonist -methylphenylaminocarbonyl)-Asp-( N-methyl)-Phe-NH2 was greater than that produced by CCK octapeptide. I n contrast, the selective CCK-B agonist [(2R,3S)-beta-MePhe28,N-MeNle3 1]CCK26-33 had no effect. These findings suggest that the growth of pu tative preneoplastic lesions (acidophilic atypical acinar cell foci an d nodules) in the rat pancreas during the early stages of azaserine-in duced pancreatic carcinogenesis is mediated specifically by way of CCK -A receptors.