Na(+)-H+ exchange is not important for pancreatic HCO3- secretion in the pig.
Pancreatic inter- and intralobular duct cells extrude H(+)-ions to interstitial fluid when they secrete HCO3- to pancreatic juice. This study assesses the potential importance of Na(+)-H(+)-ion exchange for H(+)-ion extrusion and secretion of HCO3-, using the Na(+)-H+ exchange blockers amiloride and hexamethylene-amiloride. Intracellular pH (pHi) in inter- and intralobular pancreatic duct epithelium was measured using BCECF fluorescence. H(+)-ion efflux was measured using a NH4Cl prepulse, acid-loading technique. In HCO3(-)-free media, pHi recovery following acid loading was blocked by amiloride (10(-4) M) and hexamethylene-amiloride (10(-6) M), demonstrating amiloride- and hexamethylene-amiloride-sensitive Na(+)-H+ exchange. However, 5 x 10(-6) M hexamethylene-amiloride did not reduce secretin-dependent pancreatic HCO3- secretion in vivo. Maximal H(+)-efflux through Na(+)-H+ exchange was 1.5 +/- 0.2 mumol min-1 ml cell volume-1, i.e. less than 1% of estimated net H(+)-ion efflux during HCO3- secretion.


CONCLUSIONS
amiloride- and hexamethylene amiloride sensitive Na(+)-H+ exchange is not important for secretin-dependent pancreatic HCO3- secretion in the pig. Other mechanisms for H+ extrusion dominate.
Veel
T
T
University of Oslo, Institute for Experimental Medical Research, Norway.
Villanger
O
O
Holthe
M R
MR
Cragoe
E J
EJ
Raeder
M G
MG
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D066298:In Vitro Techniques; D007474:Ion Exchange; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D011522:Protons; D012633:Secretin / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers; D013552:Swine
D001639:Bicarbonates; D002352:Carrier Proteins; D011522:Protons; D017923:Sodium-Hydrogen Exchangers; D012633:Secretin; D000584:Amiloride; D012964:Sodium