Secretin stimulates bile ductules to secrete both H+ and HCO3(-)-ions.
Secretin-dependent ductular HCO3- secretion into bile may involve secretion of H+ to interstitial fluid and HCO3- to bile by the ductular epithelium. To determine whether secretin causes bile ductules to secrete H+, we have examined the effect of secretin on the elimination of an intracellular acid load from bile ductular epithelium during pharmacological blockade of Na(+)-H+ exchange and in the absence of HCO3-. Microdissected bile ductules from pigs were suspended in HCO3- free HEPES buffer and loaded with acid using an NH4Cl prepulse technique. Intracellular pH was measured using dual-wavelength excitation of BCECF fluorescence. Na(+)-H+ exchange was defined as a Na(+)-dependent and amiloride- and 5-(N,N-hexamethylene)-amiloride-sensitive efflux of H(+)-ions following acid loading. We found that secretin stimulated ductular H+ secretion independent of Na(+)-H+ exchange. Blockade of Na(+)-H+ exchange by hexamethylene-amiloride did not affect secretin-dependent ductular HCO3- choleresis in vivo. We conclude that secretin stimulates bile ductules to secrete H(+)-ions to interstitial fluid as well as HCO3- ions to bile by a mechanism independent of Na(+)-H+ exchange.
Villanger
O
O
University of Oslo, Institute for Experimental Medical Research, Norway.
Veel
T
T
Holthe
M R
MR
Cragoe
E J
EJ
Raeder
M G
MG
D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D001652:Bile Ducts / Q000187:drug effects / Q000378:metabolism*; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D006859:Hydrogen / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007474:Ion Exchange; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D012633:Secretin / Q000494:pharmacology*; D013268:Stimulation, Chemical; D013552:Swine
D001639:Bicarbonates; D012633:Secretin; C057360:5-(N,N-hexamethylene)amiloride; D000584:Amiloride; D006859:Hydrogen