Histamine H1- and H2-receptor blockade does not maintain electrochemical gradients across canine gastric mucosa exposed to bile salt.
We tested the hypothesis that histamine mediates the changes in cation permeability and potential difference characteristics of gastric mucosal barrier disruption. Canine Heidenhain pouches were exposed to 20 mM sodium taurocholate both with and without combined histamine H1- and H2-receptor blockade with diphenhydramine 2 mg/kg and metiamide 10 mumol (2.5 mg)/kg/hr. Histamine-receptor blockade did not attenuate the flux, clearance rate, or permeability of hydrogen ion due to bile salt exposure and had no effect on the fluxes of sodium, chloride, and volume. Although the potential difference was higher with combined histamine-receptor blockade, the fall in potential difference due to bile salt was not attenuated. Using a pH-stat system to measure acid loss with the incremental addition of sodium taurocholate to final concentrations of 0, 5, 10, and 20 mM, we failed to observe any difference between control and histamine-receptor blockade in hydrogen flux or permeability. Increases in gastric blood flow due to intraarterial injection of histamine were attenuated with diphenhydramine, 2 mg/kg. Further attenuation of this vasodilation was observed with the addition of a histamine H2 antagonist but not with increasing the dose of the H1 antagonist to 10 mg/kg. Thus we were unable to document that doses sufficient to antagonize histamine H1 and H2 receptors prevent the increase in sodium-hydrogen flux and decrease in potential difference observed with exposure of the canine stomach to bile salt.
D000818:Animals; D001647:Bile Acids and Salts / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects; D004155:Diphenhydramine / Q000494:pharmacology; D004285:Dogs; D004563:Electrochemistry; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects*; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D008785:Metiamide / Q000494:pharmacology; D013656:Taurocholic Acid / Q000494:pharmacology
D001647:Bile Acids and Salts; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D008785:Metiamide; D013656:Taurocholic Acid; D004155:Diphenhydramine