Hyperosmolarity evokes histamine release from ileum mucosa by stimulating a cholinergic pathway.

Changes in extracellular osmolarity lead to alteration in cellular volume. In the study, we examined the effects of hyperosmolarity on short-circuit currents (Isc) in the rat ileum using the Ussing chamber technique. Mucosal exposure to 20 mM glucose evoked a decrease of I in the rat ileum, which was antagonized by the stretch-activated channel blocker GdCl3, TTX and atropine, respectively. In contrast, it was not blocked by phlorizin, a Na-glucose cotransporter SGLT1 inhibitor. Furthermore, the unabsorbed substances, such as sucrose, lactulose or urea, also induced a decrease of I in rat ileum. ELISA results revealed that 20 mM glucose stimulated the release of histamine from rat ileum mucosa, which was attenuated by TTX. In addition, the glucose-induced I was depressed by pyrilamine, a histamine H receptor blocker (H antagonist) whereas it was not affected by ranitidine (H antagonist), clobenpropit (H antagonists) or JNJ7777120 (H antagonist), respectively. The ion substitution experiments suggest that the changes of Na and HCO ion flux underlie the glucose-induced I In conclusion, osmotic stimulus decreased the basal I of rat ileum by evoking histamine release from ileum mucosa. The changes of Na and HCO ion transport are involved in the glucose-evoked decrease of basal I.