title: Stimulation of growth of azaserine-induced putative preneoplastic lesions in rat pancreas is mediated specifically by way of cholecystokinin-A receptors.
abstract: 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.
authors.affiliation: Department of Surgery, University of Cincinnati College of Medicine, Ohio 45267.
authors.forename: S P
authors.initials: SP
authors.lastname: Povoski
authors.forename: W
authors.initials: W
authors.lastname: Zhou
authors.forename: D S
authors.initials: DS
authors.lastname: Longnecker
authors.forename: B D
authors.initials: BD
authors.lastname: Roebuck
authors.forename: R H
authors.initials: RH
authors.lastname: Bell
mesh_terms: D000818:Animals; D001377:Azaserine; D002766:Cholecystokinin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002908:Chronic Disease; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010179:Pancreas / Q000187:drug effects / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000139:chemically induced / Q000473:pathology*; D010195:Pancreatitis / Q000139:chemically induced; D010446:Peptide Fragments / Q000494:pharmacology*; D011230:Precancerous Conditions / Q000139:chemically induced / Q000473:pathology*; D051381:Rats; D011917:Rats, Inbred Lew; D011949:Receptors, Cholecystokinin / Q000502:physiology*; D012844:Sincalide / Q000494:pharmacology*; D013758:Tetragastrin / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D010446:Peptide Fragments; D011949:Receptors, Cholecystokinin; D013758:Tetragastrin; C066278:A 71623; C082766:SNF 8815; D001377:Azaserine; D002766:Cholecystokinin; D012844:Sincalide