Histamine is released into the systemic circulation in many pathological situations and needs to be cleared rapidly to prevent intoxication. The present study aimed to elucidate the mechanisms of histamine clearance in the gut. Flux studies with 3H-histamine were performed with colonic epithelia of pig mounted in Ussing chambers. Under gradient-free conditions, net secretion of radioactivity (hist-rad) occurred and was inhibited by serosal addition of 1-methyl-4- phenylpyridinium. After unilateral addition of 3H-histamine to the serosal side, only 22.6 ± 7.8% of the hist-rad sm flux was non- degraded histamine; the remaining part was catabolites. However, catabolites appearing on the mucosal side contained no 1- methylhistamine (1-MH). Instead, 1-MH was recycled to the serosal buffer solution in a quantity exceeding the histamine flux to the mucosal buffer solution. The histamine flux to the mucosal solution was inhibited by amodiaquin and aminoguanidin, while the serosal recycling of 1-MH was inhibited by amodiaquin and N-ethylmaleimide. Poly-A+ RNA was demonstrated for organic cation transporter 1 (OCT1) and the vesicular monoamine transporter 2 (VMAT2). After active import across the basolateral membrane, histamine is subject to intracytoplasmic inactivation by histamine N- methyltransferase and intravesicular inactivation by diamine oxidase. 1-MH can leave the cells on the basolateral side only.

The study was supported in part by the DFG (AS 131/1-3)