Effect of histamine H2 antagonism by metiamide on the response of the canine gastric mucosa to acid and bile salt.
Prevention of acute gastric erosions with histamine H2-receptor blocking agents suggests that these drugs may improve the ability of the gastric mucosa to maintain electrical, ionic, and protein concentration gradients. In 5 awake mongrel dogs, transmural potential difference, ion fluxes, and protein loss were measured across Heidenhain pouches topically exposed to isotonic solutions containing either 80 mM HCl or 80 mM HCl plus 20 mM sodium taurocholate (BS). The dogs received an intravenous infusion of either saline (as a control) or the H2 antagonist metiamide, 10 mumoles per kg-hr. Metiamide increased the H+ clearance rate found after acid test solution exposure but had no significant effect on potential difference or ion fluxes. H2 antagonism decreased the protein loss but not the increase in cation permeability due to BS. Net H+ loss actually increased, which, along with a decrease in Cl- gain, suggests inhibition of acid secretion by metiamide in BS-exposed gastric mucosa. These effects of metiamide point to histamine as a likely mediator of the gastric mucosal damage due to BS.
D000818:Animals; D002463:Cell Membrane Permeability / Q000187:drug effects; D004285:Dogs; D005745:Gastric Acidity Determination; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D006851:Hydrochloric Acid; D008785:Metiamide / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D013276:Stomach Ulcer / Q000139:chemically induced*; D013656:Taurocholic Acid; D013890:Thiourea / Q000031:analogs & derivatives*
D008785:Metiamide; D013656:Taurocholic Acid; D012964:Sodium; D013890:Thiourea; D006851:Hydrochloric Acid; D011188:Potassium