title: Vasoactive intestinal peptide control of cyclic adenosine 3':5'-monophosphate levels in seven human colorectal adenocarcinoma cell lines in culture.
abstract: This study was undertaken to assess the role of vasoactive intestinal peptide (VIP) in the control of cyclic adenosine 3':5'-monophosphate production in colonic tumor cells. Seven human colorectal adenocarcinoma cell lines in culture were investigated (HT-29, HRT-18, SW-480, Caco-2, CO-115, CO-125, and HCT-8R). These cell-lines had a cyclic adenosine 3':5'-monophosphate production system which was very sensitive to VIP but less so to prostaglandin E1 and/or isoproterenol. Nonintestinal human malignant epithelial cells, such as HeLa (cervix) and Caki-1 and Caki-2 (kidney), by contrast, did not respond to VIP. The dose-response relationships of malignant colorectal cells were compared to those obtained with epithelial cells of normal human colon and showed that: (a) maximal responses were observed with 0.1 micro M VIP in both malignant and normal cells; (b) half-maximal responses were elicited by VIP concentrations in the 0.3 to 2 nM range in malignant cells (1.2 nM in normal cells), thus indicating the high apparent affinity of the cells to VIP; and (c) the magnitudes of the responses (stimulated:basal ratios) were highly variable in malignant cells, ranging from 225 in HT-29 cells to 3.5 in Caco-2 cells, but were more constant, in the order of 25, in normal cells. Secretin, a VIP agonist in intestinal tissue, stimulated cyclic adenosine 3':5'-monophosphate accumulation in all colorectal cells, but with a 1000- to 5000-fold lower potency than did VIP. These results show that the VIP-sensitive adenylate cyclase system operates in malignant as well as in normal colon epithelial cells.
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism*; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D003110:Colonic Neoplasms / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism*; D005768:Gastrointestinal Hormones / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D051379:Mice; D009374:Neoplasms, Experimental / Q000378:metabolism; D011458:Prostaglandins E / Q000494:pharmacology; D012004:Rectal Neoplasms / Q000378:metabolism*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
chemical_list: D005768:Gastrointestinal Hormones; D011458:Prostaglandins E; D014660:Vasoactive Intestinal Peptide; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D007545:Isoproterenol