Paracellular tightness and catabolism restrict histamine permeation in the proximal colon of pigs

Abstract

Luminal histamine concentrations can be very high in the intestine without eliciting clinical histaminosis. The intestinal mechanisms that possibly prevent systemic intoxication by luminal histamine were investigated in the present study. Porcine colonic epithelia were mounted in Ussing chambers. After unilateral application of partially (3)H-labelled histamine, mucosal-to-serosal (MS) and serosal-to-mucosal (SM) flux rates were calculated from the contralateral appearance of histamine and the radioactive histamine label (hist-rad; representing histamine plus catabolites). A discrepancy between histamine and hist-rad fluxes was observed in both flux directions, indicating efficient histamine catabolism at all histamine concentrations tested (5, 50 and 100 microM). Catabolism exceeded 65% at 100 microM histamine and reached approximately 100% at 5 microM histamine. Blockade of histamine N-methyltransferase by amodiaquin (100 microM) abolished catabolism completely, whereas blockade of diamine oxidase by aminoguanidine (100 microM) was less effective. MS fluxes of histamine and hist-rad correlated with mannitol fluxes. Mast cell stimulation with the calcium ionophore A23187 (1 microM) induced a twofold larger histamine appearance on the serosal side than the mucosal application of 100 microM histamine. It is concluded that histamine permeation across the porcine proximal colon is restricted by low permeability and sequential catabolism by histamine N-methyltransferase and diamine oxidase.