title: Mast cells and histamine contribute to bile acid-stimulated secretion in the mouse colon.
abstract: Certain dihydroxy bile acids cause secretory diarrhea when present in the colonic lumen at inappropriately high concentrations. However, the mechanism underlying the secretagogue activity has not been fully elucidated. Experiments were performed to test whether mast cells and one of their major mediators, histamine, might contribute to the secretory effect. Chenodeoxycholic acid, a secretory bile acid, and ursodeoxycholic acid, a nonsecretory, hydrophilic bile acid, were compared for their ability to induce chloride secretion across segments of mouse colon mounted in Ussing chambers. Chenodeoxycholic acid, but not ursodeoxycholic acid, induced dose-dependent, biphasic chloride secretion that was greater after serosal than mucosal addition and was greater in distal versus proximal colonic segments. The secretory effect of chenodeoxycholic acid was inhibited by H1 histamine receptor antagonists and modified by the cyclooxygenase inhibitor indomethacin. However, it was unaffected by an H2 histamine receptor antagonist or by atropine. Secretory effects of chenodeoxycholic acid were diminished in magnitude and delayed in colonic tissues from mice with a genetic deficiency of tissue mast cells. Concentrations of chenodeoxycholic acid inducing secretion also released histamine from tissue segments. These data indicate that mast cells and histamine-mediated processes contribute significantly to the secretory effects of dihydroxy bile acids in the murine colon.
authors.affiliation: Department of Medicine, University of California, San Diego, School of Medicine 92103, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Gelbmann
authors.forename: C D
authors.initials: CD
authors.lastname: Schteingart
authors.forename: S M
authors.initials: SM
authors.lastname: Thompson
authors.forename: A F
authors.initials: AF
authors.lastname: Hofmann
authors.forename: K E
authors.initials: KE
authors.lastname: Barrett
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000502:physiology*; D001692:Biological Transport / Q000187:drug effects; D002635:Chenodeoxycholic Acid / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism; D003106:Colon / Q000378:metabolism*; D003967:Diarrhea / Q000503:physiopathology*; D006632:Histamine / Q000502:physiology*; D066298:In Vitro Techniques; D008407:Mast Cells / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D011738:Pyrilamine / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014580:Ursodeoxycholic Acid / Q000494:pharmacology; D014882:Water-Electrolyte Balance / Q000187:drug effects
chemical_list: D001647:Bile Acids and Salts; D002712:Chlorides; D002635:Chenodeoxycholic Acid; D013779:Tetrodotoxin; D014580:Ursodeoxycholic Acid; D006632:Histamine; D011738:Pyrilamine