Dihydroxy bile salt-induced alterations in NaCl transport across the rabbit colon.
The effects of increasing mucosal or serosal concentrations (1-4 mM) of taurochenodeoxycholate (TCDC) on sodium chloride transport across the isolated, short-circuited rabbit colon were examined. Mucosal TCDC produced dose-related increases in tissue conductance (Gt) and the unidirectional fluxes of Na+ and Cl- and dose-related decreases in net NaCl absorption. At 4 mM mucosal TCDC, Gt was increased fivefold, net sodium flux (JNanet) was reduced 50%, and JClnet was abolished. Serosal TCDC also produced dose-dependent changes in permeability that were quantitatively different. Four millimolar serosal TCDC produced a 2.7-fold increase in Gt, abolished JNanet, and stimulated electrogenic Cl- secretion. TCDC-induced Cl- secretion was stimulated by 10(-5) M serosal TCDC, inhibited by serosal furosemide or ouabain, did not alter theophylline-induced secretion (and vice versa), and occurred in the absence of serosal Ca2+. It is suggested that 1) TCDC inhibition of sodium absorption is indirect (i.e., not simply due to a reduction in the activity of the Na "pump," since Cl- secretion persists during conditions that abolish JNanet) and 2) TCDC induces Cl- secretion by enhancing the activity of basolateral membrane adenylate cyclase.
D000818:Animals; D002635:Chenodeoxycholic Acid / Q000031:analogs & derivatives*; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D011817:Rabbits; D012965:Sodium Chloride / Q000378:metabolism*; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology*
D002635:Chenodeoxycholic Acid; D012965:Sodium Chloride; D013655:Taurochenodeoxycholic Acid