IgE-induced degranulation of mucosal mast cells is negatively regulated via nicotinic acetylcholine receptors.
The autonomic nervous system is known to mediate mast cell activation. We investigated expression of nicotinic acetylcholine receptors (nAChRs) in mucosal-type mast cells and their contribution to the regulation of mast cell activation. Expression of mRNA of nAChR alpha4, alpha7, and beta2 subunits were detected in specially differentiated mucosal-type murine bone marrow-derived mast cells (mBMMCs). Pretreatment with non-specific nAChRs agonists, acetylcholine, nicotine and epibatidine and a specific alpha7 subunit agonist GTS-21 significantly inhibited antigen-induced degranulation of mBMMCs in a dose-dependent manner and GTS-21-induced inhibition was significantly blocked by alpha7 subunit antagonist, alpha-bungarotoxin. Furthermore, confocal microscopy also demonstrated surface binding of alpha-bungarotoxin on mBMMCs. Our findings indicate that mucosal mast cell activation may be negatively regulated mainly through nAChR alpha7 subunit, suggesting that nAChRs are involved in neuronal-mucosal mast cell interactions.
Kageyama-Yahara
Natsuko
N
Department of Bioscience, Division of Gastrointestinal Pathophysiology, Institute of Natural Medicine, University of Toyama, Sugitani, Toyama, Japan. natsuko@inm.u-toyama.ac.jp
Suehiro
Yoko
Y
Yamamoto
Takeshi
T
Kadowaki
Makoto
M
D000818:Animals; D001597:Benzylidene Compounds / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000378:metabolism / Q000502:physiology; D002038:Bungarotoxins / Q000737:chemistry / Q000494:pharmacology; D015550:Cell Degranulation; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry; D007073:Immunoglobulin E / Q000276:immunology / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000378:metabolism / Q000502:physiology*; D008407:Mast Cells / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D018722:Nicotinic Agonists / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D064569:alpha7 Nicotinic Acetylcholine Receptor
D001597:Benzylidene Compounds; D002038:Bungarotoxins; D016650:Fluorescein-5-isothiocyanate; D007073:Immunoglobulin E; D018722:Nicotinic Agonists; D011725:Pyridines; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C579166:Chrna7 protein, mouse; C088936:3-(2,4-dimethoxybenzylidene)anabaseine