Calcium ionophore activity of intestinal secretory compounds. An in vitro porcine model for the effects of bile acids, hydroxy-fatty acids and dioctyl sulfosuccinate.
The association between reported intestinal fluid secretory activity of bile acids and Ca2+ ionophore properties was investigated in a pig jejunal brush border vesicle system. Secretory and nonsecretory bile acids and hydroxy-fatty acids were tested to see if Ca2+ ionophore activity is a general property of all bile acids and hydroxy-fatty acids, or if it is confined to compounds with recognized fluid secretory activity. Ionophore activity was attributed to compounds which could increase rates of Ca2+ influx and efflux from brush border vesicles under conditions where nonspecific permeability to sorbitol was not affected. The recognized secretory agents chenodeoxycholate and dioctyl sulfosuccinate had Ca2+ ionophore activity in the test system. The nonsecretory agents cholate, hyodeoxycholate and 4-hydroxybutyrate had no detectable activity, while ursodeoxycholate showed minor ionophore activity. Due to complications resulting from Ca2+ sequestration it was impossible to determine the Ca2+ ionophore activity of 12-hydroxystearate in this system. The detergent properties of all these agents are known to increase intestinal permeability, but detergent strength, as measured by concentration required to increase mannitol exchange across vesicle membranes, did not correlate well with secretory activity. We conclude that intestinal fluid secretion caused by bile acids and hydroxy-fatty acids could be controlled partially by Ca2+ ion interactions which could include intracellular signal effects of Ca2+ on anion permeability of the brush border membrane as well as possible increases in permeability of the tight junctions, and local hypertensive effects.
D000818:Animals; D001647:Bile Acids and Salts / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000187:drug effects; D002635:Chenodeoxycholic Acid / Q000494:pharmacology; D004143:Dioctyl Sulfosuccinic Acid / Q000494:pharmacology*; D005227:Fatty Acids / Q000494:pharmacology*; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism; D007419:Intestinal Secretions / Q000378:metabolism*; D007476:Ionophores / Q000378:metabolism*; D007700:Kinetics; D008871:Microvilli / Q000378:metabolism; D013386:Succinates / Q000494:pharmacology*; D013552:Swine
D001647:Bile Acids and Salts; D005227:Fatty Acids; D007476:Ionophores; D013386:Succinates; D002635:Chenodeoxycholic Acid; D004143:Dioctyl Sulfosuccinic Acid; D002118:Calcium