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

Whereas intraruminal histamine does not affect healthy ruminants, histamino sis is apparent during ruminal acidosis. We therefore investigated the fact ors that, under physiological circumstances, prevent intoxication by intrar uminal histamine and the disturbances occurring during acidotic or hypoxic epithelial damage. After mucosal (m) or serosal (s) application of 80 mu M histamine, its flux across the isolated epithelia of the sheep rumen was de termined radioactively (hist-rad flux) in Ussing chambers. The non-cataboli zed component of the hist-rad fluxes was determined by high-pressure liquid chromatography (HPLC) (histamine flux). The difference between hist-rad an d histamine fluxes indicated efficient intraepithelial catabolism of histam ine 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 hista mine was indicated by differences between m-s and s-m fluxes of histamine a nd/or hist-rad. Epithelial permeability to hist-rad and mannitol was simila r and their fluxes correlated partly. Epithelial release of endogenous hist amine was 1.5 pmol.cm(-2).h(-1) and was not increased by the mast cell stim ulator, compound 48/80 (10 ng.ml(-1)). We conclude that histamine absorptio n across the intact epithelium is efficiently restricted by a low permeabil ity to histamine in combination with catabolic and secretory processes. Esp ecially increases in paracellular permeability and/or inhibition of catabol ism enhance histamine absorption.