Relationship of hydrogen ion back-diffusion to histamine liberation from canine oxyntic mucosa.

Pharmacological damage to gastric mucosa results in excessive movement of hydrogen out of the lumen and increased movement of sodium and potassium into the lumen. It has been previously reported that one consequence of H+ back-diffusion is the release of intramucosal histamine which probably adds to the damage by increasing capillary permeability and edema formation. In the present study histamine concentration in the solution irrigating an isolated pouch of the gastric fundus was measured following 15% (w/v) ethanol (EtOH) in either 100 mM HCl, 10 mM HCl, or 0.03 M phosphate buffer. All three solutions effectively broke the mucosal barrier as evidenced by increased net fluxes of sodium and potassium. Significant (P less than 0.05) increases in the histamine content of the fluid irrigating the pouch were observed after all treatments. The histamine output in response to EtOH in acidic solution was significantly greater than the response to EtOH at neutral pH. Instillation of 150, 200, 225, or 250 mM HCl alone into the pouch resulted in progressive increases in H+ back-diffusion. Application of 250 mM HCl alone resulted in a proportionally greater back-diffusion of H+, increases in Na+ and K+ fluxes indicating barrier damage, and the appearance of histamine. These results indicate that the damaging agent ethanol probably acts at two points: (1) it breaks the mucosal barrier, and (2) it liberates histamine. These results suggest that an increase in H+ back-diffusion per se is not solely responsible for gastric mucosal histamine liberation but that histamine is released as a general consequence of breaking the gastric mucosal barrier.