EFFECT OF MOLECULAR-STRUCTURE ON BILE ACID-INDUCED ALTERATIONS IN ABSORPTIVE FUNCTION, PERMEABILITY, AND MORPHOLOGY IN THE PERFUSED RABBIT COLON

  • 1 January 1979
    • journal article
    • research article
    • Vol. 94  (5) , 661-674
Abstract
An in vivo intestinal perfusion system was used to study the effects of different bile acids on fluid secretion, mucosal permeability and mucosal morphology in the rabbit colon. To define the structure-activity relationships of the bile acids, 9 unconjugated bile acids were used, varying only in the number (2 or 3) or position (3, 7, 12 or various combinations) of hydroxy or keto nuclear substituents. Bile acids with 2 hydroxy groups in the .alpha. configuration at the 3,7 position, 3,12 position or 7,12 position induced fluid secretion, increased mucosal permeability and produced mucosal damage as assessed by light and scanning electron microscopy and quantitated by DNA loss during perfusion. Replacement of hydroxy groups by keto groups or a change from .alpha. to .beta. configuration for the hydroxylic substituent in the 7 position abolished all 3 activities. Trisubstituted derivatives, whether hydroxy or keto, did not affect fluid secretion permeability or cause mucosal damage. Of the major primary and secondary bile acids in man, only deoxycholic and chenodeoxycholic acids alter colonic structure and function in the rabbit. The cathartic effects of bile acids have specific structural requirements and bile acid-induced secretion was invariably associated with increased mucosal permeability and epitheliolysis.