Acid-induced increase in electrical conductance of guinea pig duodenal mucosa in vitro. Temporary protection by combined effects of bicarbonate and prostaglandin E2.
Electrical conductance as a sensitive indicator of acid damage has been investigated in guinea pig duodenal mucosa using Ussing-chamber techniques. Reductions of luminal pH from 7.4 to 3.0, 2.3, or 2.0 caused concentration-dependent, progressive increases in conductance, accompanied (pH 2.0) by a continuous increase in hydrogen permeation as determined by pH-stat titration. Increases in conductance and hydrogen flux were related to base-line conductance, with higher values conditioning for a sooner onset and/or more marked elevation. Conductance increases were prevented by timely back titration. Recently, it has been shown that serosal HCO3 reduces conductance by actions dependent on prostaglandins and serosal Na and sensitive to loop diuretics. Here, serosal HCO3 delayed the onset of acid-induced conductance increase by approximately 8 minutes, an effect reduced by omission of serosal Na and during exposure to serosal furosemide (10(-3) mol/L). In the presence of serosal indomethacin (10(-4) mol/L) and HCO3, prostaglandin E2 (10(-6) mol/L serosal bath) delayed the conductance increase. Because HCO3 secretion is negligible in this model, these results indicate effects of HCO3/prostaglandin E2 beyond mere buffering of invading hydrogen. These results are consistent with intracellular actions that tighten the paracellular pathway against acid and thus provide temporary protection from acid injury. In agreement with this view, HCO3 also limited conductance increases after luminal alkalinization by a furosemide-sensitive action.
Macherey
H J
HJ
Institut für Pharmakologie, Medizinischen Fakultät, Rheinisch-Westfälische Technische Hochschule Aachen, Wendlingweg, Germany.
Petersen
K U
KU
D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology*; D015232:Dinoprostone / Q000502:physiology*; D004386:Duodenum / Q000378:metabolism / Q000502:physiology*; D004553:Electric Conductivity / Q000187:drug effects*; D005665:Furosemide / Q000494:pharmacology; D006168:Guinea Pigs; D006851:Hydrochloric Acid / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000378:metabolism / Q000502:physiology*; D008297:Male; D012964:Sodium / Q000502:physiology; D012972:Sodium Hydroxide / Q000494:pharmacology
D001639:Bicarbonates; D012972:Sodium Hydroxide; D005665:Furosemide; D012964:Sodium; D015232:Dinoprostone; D006851:Hydrochloric Acid; D007213:Indomethacin