Mast cell expression of the serotonin_1Areceptor in guinea pig and human intestine

Abstract

] is released from enterochromaffin cells in the mucosa of the small intestine. We tested a hypothesis that elevation of 5-HT in the environment of enteric mast cells might degranulate the mast cells and release mediators that become paracrine signals to the enteric nervous system, spinal afferents, and secretory glands. Western blotting, immunofluorescence, ELISA, and pharmacological analysis were used to study expression of 5-HT receptors by mast cells in the small intestine and action of 5-HT to degranulate the mast cells and release histamine in guinea pig small intestine and segments of human jejunum discarded during Roux-en-Y gastric bypass surgeries. Mast cells in human and guinea pig preparations expressed the 5-HT1A receptor. ELISA detected spontaneous release of histamine in guinea pig and human preparations. The selective 5-HT1A receptor agonist 8-hydroxy-PIPAT evoked release of histamine. A selective 5-HT1A receptor antagonist, WAY-100135, suppressed stimulation of histamine release by 5-HT or 8-hydroxy-PIPAT. Mast cell-stabilizing drugs, doxantrazole and cromolyn sodium, suppressed the release of histamine evoked by 5-HT or 8-hydroxy-PIPAT in guinea pig and human preparations. Our results support the hypothesis that serotonergic degranulation of enteric mast cells and release of preformed mediators, including histamine, are mediated by the 5-HT1A serotonergic receptor. Association of 5-HT with the pathophysiology of functional gastrointestinal disorders (e.g., irritable bowel syndrome) underlies a question of whether selective 5-HT1A receptor antagonists might have therapeutic application in disorders of this nature. enteric mast cells; histamine; enteric nervous system; functional gastrointestinal disorders; irritable bowel syndrome MAST CELLS ARE PRESENT in continuously varying numbers in the intestinal mucosa, lamina propria, and smooth muscle coats. Mast cell numbers expand in parasitic nematode infections and are major factors associated with inflammation-related changes in Clostridium difficile and other bacterial infections (5, 52). Increased numbers of enteric mast cells are associated with inflammatory responses in general (e.g., radiation-induced inflammation) (36). In humans, numbers of enteric mast cells are elevated in diarrhea-predominant irritable bowel syndrome (D-IBS) relative to healthy controls (1,9,40,41). Moreover, elevated mast cell numbers contribute to release of greater amounts of the preformed mast cell mediator histamine from mucosal biopsies removed from patients with postinfectious D-IBS (1). Increased concentrations of histamine in the incubation medium, in these cases, evoke higher frequencies of firing of secretomotor neurons when applied to preparations from the submucosal plexus of guinea pigs in vitro (6, 7).Enteric mast cells release two kinds of mediators (44). Preformed mediators are stored in cytoplasmic granules and released when the mast cells discharge the granules into the extracellular environment. Examples of preformed mediators are histamine and serine ...

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β-Nicotinamide adenine dinucleotide acts at prejunctional adenosine A1 receptors to suppress inhibitory musculomotor neurotransmission in guinea pig colon and human jejunum

“…Methods for procurement of tissues for the in vitro studies are described elsewhere (53,57). Male Hartley-strain guinea pigs (300 -400 g body wt) were obtained from Charles River (Wilmington, MA).…”

“…Segments of small intestine and colon for muscle bath studies and for electrophysiology were obtained by microdissection from guinea pigs. Fresh preparations of healthy human small intestine were obtained from segments of jejunum discarded during Roux-en-Y gastric bypass surgeries, as described elsewhere (53,57). The human protocols were approved by the Institutional Review Board of The Ohio State University Office of Research Risks Protection (protocol 02H0208).…”

Relation between mast cells concentration and serotonin expression in chagasic megacolon development

“…Thus, these cells maintain the architecture of the intestinal epithelium by regulating epithelial migration . Besides, serotonin (5‐hydroxytryptamine or 5‐HT) produced by enterochromaffin cells in the intestine and histamine produced by mucosal mast cells acts as a proinflammatory mediator in the intestine and modulate intestinal permeability …”