Mast cells and histamine contribute to bile acid-stimulated secretion in the mouse colon.

Abstract

Certain dihydroxy bile acids cause secretory diarrhea when present in the colonic lumen at inappropriately high concentrations. However, the mechanism underlying the secretagogue activity has not been fully elucidated. Experiments were performed to test whether mast cells and one of their major mediators, histamine, might contribute to the secretory effect. Chenodeoxycholic acid, a secretory bile acid, and ursodeoxycholic acid, a nonsecretory, hydrophilic bile acid, were compared for their ability to induce chloride secretion across segments of mouse colon mounted in Ussing chambers. Chenodeoxycholic acid, but not ursodeoxycholic acid, induced dose-dependent, biphasic chloride secretion that was greater after serosal than mucosal addition and was greater in distal versus proximal colonic segments. The secretory effect of chenodeoxycholic acid was inhibited by H1 histamine receptor antagonists and modified by the cyclooxygenase inhibitor indomethacin. However, it was unaffected by an H2 histamine receptor antagonist or by atropine. Secretory effects of chenodeoxycholic acid were diminished in magnitude and delayed in colonic tissues from mice with a genetic deficiency of tissue mast cells. Concentrations of chenodeoxycholic acid inducing secretion also released histamine from tissue segments. These data indicate that mast cells and histamine-mediated processes contribute significantly to the secretory effects of dihydroxy bile acids in the murine colon. (J. Clin. Invest. 1995. 95:2831-2839

Effect of cholic acid on colonic motility in mice

“…In these experiments, CA inhibited PMC amplitude after addition of 5-HT3 antagonist, 5-HT4 antagonist and H1 anta-gonist. These results were in agreement with previous studies which demonstrated that BAs are able to activate mast cells (Gelbmann et al, 1995;Fihn et al, 2003) and act via 5-HT3 receptor. Therefore, the inhibition of CA in the presence of histamine antagonist on PMCs suggested that mast cells are playing an important role in mediating hyperexcitability and enteric neuron depolari-zation via their release of histamine from mast cell degranulation (Sand et al, 2009).…”

Intestinal bile acid physiology and pathophysiology

“…It is well known that BAs elicit fluid secretion and also increased permeability in the gastrointestinal tract [97][98][99][100][101] . BAs also affect intestinal motility, although this field of study has received relatively little attention [1,102] .…”

“…This effect is to a large extent indirect, induced by intramural reflexes containing nicotinic receptors, but probably it does not involve histamine or nitric oxide pathways [97,103,104] . However, this question is controversial, because in some cases histamine has been suggested to be involved [98] . The secretory effect of BAs has been studied in the small and large intestine, and in both cases the mechanism of secretion appears to be largely indirect [99] .…”

“…On the other hand, in the colon BA-induced secretion has been claimed to be prostaglandin dependent [106] . More specifically, prostaglandins may account for the early response to BA stimulation observed in vitro [98] . Mast cells have also been involved in this process [98] .…”

“…More specifically, prostaglandins may account for the early response to BA stimulation observed in vitro [98] . Mast cells have also been involved in this process [98] . Indeed, BAs have been shown to induce prostaglandin [107] and histamine secretion [108] in vitro.…”