Transport, catabolism and release of histamine in the ruminal epithelium of sheep

Whereas intraruminal histamine does not affect healthy ruminants, histaminosis is apparent during ruminal acidosis. We therefore investigated the factors that, under physiological circumstances, prevent intoxication by intraruminal histamine and the disturbances occurring during acidotic or hypoxic epithelial damage. After mucosal (m) or serosal (s) application of 80 µM histamine, its flux across the isolated epithelia of the sheep rumen was determined radioactively (hist-rad flux) in Ussing chambers. The non-catabolized component of the hist-rad fluxes was determined by high-pressure liquid chromatography (HPLC) (histamine flux). The difference between hist-rad and histamine fluxes indicated efficient intraepithelial catabolism of histamine at pH 7.4 (m-s direction, 98.7%; s-m direction, 93.3%). Both 0.1 mM 2,4-dinitrophenol (DNP) and mucosal acidification to pH 5.1 increased hist-rad fluxes and decreased catabolic efficiency. pH-dependent secretion of histamine was indicated by differences between m-s and s-m fluxes of histamine and/or hist-rad. Epithelial permeability to hist-rad and mannitol was similar and their fluxes correlated partly. Epithelial release of endogenous histamine was 1.5 pmol·cm–2·h–1 and was not increased by the mast cell stimulator, compound 48/80 (10 ng·ml–1). We conclude that histamine absorption across the intact epithelium is efficiently restricted by a low permeability to histamine in combination with catabolic and secretory processes. Especially increases in paracellular permeability and/or inhibition of catabolism enhance histamine absorption.