Transcellular bicarbonate transport in rabbit gallbladder epithelium: mechanisms and effects of cyclic AMP |
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Authors: | K. -U. Petersen F. Wehner J. M. Winterhager |
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Affiliation: | (1) Institut für Pharmakologie der Medizinischen Fakultät, Rheinisch-Westfälische Technische Hochschule Aachen, D-5100 Wendlingweg, Aachen, Federal Republic of Germany;(2) Present address: Max-Planck-Institut für Systemphysiologie, Rhein-landdamm 201, D-4600 Dortmund 1, Federal Republic of Germany |
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Abstract: | HCO3 permeation through rabbit gallbladder epithelium has been investigated in vitro using voltage-clamp, pH-stat and microelectrode techniques. Mucosa-to-serosa flux of HCO3 ( 4.9 mol cm–2h–1) was dependent on luminal Na and inhibited by amiloride (1 mmol/l, luminal bath), methazolamide (0.1 mmol/l, both sides), and ouabain (30 mol/l, serosal bath). Maximal rates of serosa-to-mucosa flux of HCO3 ( 2.8 mol cm–2h–1) required serosal Na and mucosal Cl. This flux was inhibited by ouabain, 4-acetamido-4 -isothiocyanato-stilbene-2,2 -disulfonic acid (1 mmol/l, serosal bath), and 5-nitro-2-(3-phenylpropylamino)-benzole acid (0.1 mmol/l, luminal bath). Ineffective were methazolamide (0.1 mmol/l, both sides) and amiloride (1 mmol/l, serosal bath). 8-Br-cAMP (1 mmol/l, serosal bath) largely inhibited the absorptive and moderately stimulated the secretory flux. In tissue conductance, short-circuit current, and transmural voltage prostaglandin E1 (1 mol/l, serosal bath) and 8-Br-cAMP caused moderate to negligible increases. No significant alterations of apical membrane potential ( –65 mV) and the apparent ratio of membrane resistances (Ra/Rb; 1.9) were found. Cell membranes responded to luminal Cl removal mostly with a slow hyperpolarization that was mitigated by 8-Br-cAMP or, in some cases, converted into a small, transient depolarization. Our results are best explained by transcellular HCO3 transport in both directions. In secretion, basolateral HCO3 entry occurs by some form of co-transport with Na, and apical exit by Cl/HCO3 exchange. cAMP opens no major electrodiffusive pathway for apical anion efflux. In absorption, HCO3 import from the lumen into the cell is secondary to cAMP-sensitive Na/H exchange. |
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Keywords: | Amiloride Cl permeability membrane voltages methazolamide NPPB SITS |
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