Histamine inactivation in the colon of pigs in relationship to abundance of catabolic enzymes

Abstract

Objective. Catabolism of histamine plays a crucial role in the intestine in preventing intoxication by luminal histamine. Two enzymes are involved, namely histamine N-methyltransferase (HMT) and diamine oxidase (DAO). The purpose of this study was to find a link between histamine catabolism and the activities of HMT and DAO. Material and methods. Epithelia of porcine proximal colon were mounted in Ussing chambers. After mucosal addition of ³H-histamine (100 µmol·l⁻¹) and ¹⁴C-mannitol, the appearance of non-catabolized histamine, ³H-histamine label (hist-rad) and ¹⁴C-mannitol label were measured in parallel on the serosal side. Activities of HMT and DAO were determined in the proximal colon and proximal jejunum. Results. Differences between the fluxes of histamine and hist-rad indicated catabolic conversion of 81.4±1.6% histamine during epithelial transit. Fluxes of hist-rad and histamine increased linearly with increasing mannitol fluxes but the percentage of catabolized histamine was not related to either mannitol or hist-rad fluxes. However, the percentage of catabolized histamine rose with increasing DAO activity. Given a negative correlation between DAO and HMT activities, the fraction of catabolized histamine decreased with increasing HMT activity. HMT activity was comparable in the colon and jejunum, but DAO activity was approximately nine times higher in the jejunum. Conclusions. Permeation, but not the relative efficiency of catabolism, of histamine depends on epithelial/paracellular tightness. While previous studies have shown that colonic HMT essentially catabolizes the bulk of histamine during permeation, DAO activity seems to be more variable and limiting for the overall efficiency of the catabolic process.