Rapid decrease in electrical conductance of mammalian duodenal mucosa in vitro. Combined effects of prostaglandin E2 and bicarbonate.
The effects of HCO3- on transepithelial conductance of guinea pig (and, in some experiments, rabbit) duodenum have been investigated using stripped preparations in Ussing-type chambers. Initial conductance amounted to approximately 27 mS/cm2. In the presence of serosal or bilateral HCO3- (20 mM), it fell to approximately 15 mS/cm2 within 60 min. With mucosal HCO3- or HCO3- -free solutions, conductance decreased to only approximately 23 mS/cm2. In the absence of HCO3-, serosal but not mucosal addition of HCO3- prompted a steep conductance drop that was 50% complete within 6 min. These effects were the same in proximal and distal segments, whereas conductance levels in the latter were higher. The effects of HCO3- required serosal Na+; they were partly prevented or reversed by serosal ouabain (3 x 10(-5) M), furosemide (10(-3) M), and other loop diuretics, and indomethacin (10(-5) M). Serosal addition of prostaglandin E2 (10(-7) M, followed by 10(-6) M) reduced conductance from approximately 22 to approximately 17 mS/cm2. This effect required serosal HCO3- and the presence of indomethacin. 8-Br-cyclic adenosine monophosphate (10(-3)M, serosal side) mimicked the effects of prostaglandin E2. Indomethacin and prostaglandin E2 did not influence the secretory flux of HCO3- (approximately 0.5 mumol/cm2.h, pH-stat method). Our results assign a critical role to serosal HCO3- in the maintenance of a low tissue permeability, dependent on the availability of prostaglandins (cyclic adenosine monophosphate) and involving HCO3- access to the cell rather than secretion.
Macherey
H J
HJ
Institut für Pharmakologie, Medizinischen Fakultät, Rheinisch-Westfälische Technische, Hochschule Aachen, Federal Republic of Germany.
Petersen
K U
KU
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology; D002478:Cells, Cultured; D015232:Dinoprostone / Q000494:pharmacology / Q000502:physiology; D004386:Duodenum / Q000502:physiology*; D004553:Electric Conductivity / Q000187:drug effects / Q000502:physiology; D006168:Guinea Pigs; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000502:physiology*; D008297:Male; D011817:Rabbits; D012964:Sodium / Q000494:pharmacology; D013997:Time Factors
D001639:Bicarbonates; D015124:8-Bromo Cyclic Adenosine Monophosphate; D012964:Sodium; D015232:Dinoprostone; D007213:Indomethacin