期刊
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
卷 467, 期 8, 页码 1809-1823出版社
SPRINGER HEIDELBERG
DOI: 10.1007/s00424-014-1609-9
关键词
Food allergy; Histamine; Histamine receptors; Intracellular Ca2+; Mast cells; Submucosal plexus
类别
资金
- Deutsche Forschungsgemeinschaft [Di 388/13-1]
Histamine is a mast cell mediator released e.g. during food allergy. The aim of the project was to identify the effect of histamine on rat submucosal neurons and the mechanisms involved. Cultured submucosal neurons from rat colon express H-1, H-2 and H-3 receptors as shown by immunocytochemical staining confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) with messenger RNA (mRNA) isolated from submucosal homogenates as starting material. Histamine evoked a biphasic rise of the cytosolic Ca2+ concentration in cultured submucosal neurons, consisting in a release of intracellularly stored Ca2+ followed by an influx from the extracellular space. Although agonists of all three receptor subtypes evoked an increase in the cytosolic Ca2+ concentration, experiments with antagonists revealed that mainly H-1 (and to a lesser degree H-2) receptors mediate the response to histamine. In coculture experiments with RBL-2H3 cells, a mast cell equivalent, compound 48/80, evoked an increase in the cytosolic Ca2+ concentration of neighbouring neurons. Like the response to native histamine, the neuronal response to the mast cell degranulator was strongly inhibited by the H-1 receptor antagonist pyrilamine and reduced by the H-2 receptor antagonist cimetidine. In rats sensitized against ovalbumin, exposure to the antigen induced a rise in short-circuit current (I (sc)) across colonic mucosa-submucosa preparations without a significant increase in paracellular fluorescein fluxes. Pyrilamine strongly inhibited the increase in I (sc), a weaker inhibition was observed after blockade of protease receptors or 5-lipoxygenase. Consequently, H-1 receptors on submucosal neurons seem to play a pivotal role in the communication between mast cells and the enteric nervous system.
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