Bioelimination of histamine in epithelia of the porcine proximal colon of pigs

Abstract.

Objective:

The study aimed to gain insight into how intestinal histamine N-methyltransferase (HMT) and diamine oxidase (DAO) could contribute to bioelimination of histamine.

Material and Methods:

Mucosal-to-serosal (ms) and serosal-to-mucosal (sm) fluxes of histamine, choline or 5-hydroxytryptamine were measured in isolated colonic epithelia of pigs (Ussing chambers).

Results:

Radioactively (hist-rad) and HPLC-measured histamine fluxes were higher in sm vs. ms direction at 100 μM histamine. Choline (3–3000 μM) and 5-HT (20 μM) fluxes only tended to be higher in sm vs. ms direction. Secretion of hist-rad was abolished by serosal 1-methyl-4-phenylpyridinium (MPP). Histamine fluxes accounted for <25 % of hist-rad fluxes, but this percentage increased after blocking HMT (100 μM amodiaquin) or DAO (100 μM aminoguanidine). 1-Methylhistamine (1-MH) appeared exclusively in the serosal medium. 1-MH appearance decreased after addition of amodiaquin or after addition of N-ethylmaleimide (1 mM NEM). Blockage of vesicular trafficking by NEM enhanced histamine catabolism, which could be reversed by aminoguanidine. DAO was detected in punctuate structures in the basal parts of colonocytes by immunohistochemistry.

Conclusions:

A basolateral organic cation transporter facilitates histamine secretion into the intestinal lumen and delivers histamine to catabolism by HMT and/or vesicular DAO. Histamine is partially released back into the blood after initial biotransformation to 1-MH.