IgE-induced degranulation of mucosal mast cells is negatively regulated via nicotinic acetylcholine receptors

Kageyama-Yahara, Natsuko; Suehiro, Yoko; Yamamoto, Takeshi; Kadowaki, Makoto

doi:10.1016/j.bbrc.2008.10.004

Cited by 69 publications

(62 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The mBMMCs were prepared from the femurs of BALB/c mice as previously described (9) with slight modification. Briefly, the bone marrow cells were cultured in RPMI-1640 medium supplemented with 40 ng/mL SCF, 20 ng/mL IL-3, 5 ng/mL IL-9 and 1 ng/mL TGF-β 1 for 3 weeks at 37°C in a humidified 5% CO 2 atmosphere.…”

Section: Resultsmentioning

confidence: 99%

“…The cells were stimulated with 1 μM A23187 for 30 min. Degranulation was assessed by measuring β-hexosaminidase release, which has been described previously (9). The extent of degranulation was calculated by dividing the β-hexosaminidase activity in the supernatant by the sum of the activity in the supernatant and cell lysate.…”

Section: Effect Of Cgrp On Mbmmcsmentioning

confidence: 99%

See 1 more Smart Citation

CGRP, a neurotransmitter of enteric sensory neurons, contributes to the development of food allergy due to the augmentation of microtubule reorganization in mucosal mast cells

et al. 2014

Self Cite

View full text Add to dashboard Cite

Neuro-immune interaction in the gut is substantially involved in the maintenance of intestinal immune homeostasis and the pathology of intestinal immune diseases. We have previously demonstrated that mucosal mast cells and nerve fibers containing CGRP, a neurotransmitter of intrinsic enteric sensory neurons, are markedly increased and exist in close proximity to each other in the colon of food allergy (FA) mice. In the present study, a CGRP-receptor antagonist BIBN4096BS significantly alleviated allergic symptoms in the murine FA model. In addition, the elevated numbers of mucosal mast cells in the proximal colon of FA mice were significantly decreased in that of BIBN4096BS-treated FA mice. Thus, we investigated the effects of CGRP on calcium-independent process in degranulation of mucosal mast cells since CGRP increases intracellular cAMP levels, but not Ca 2+ concentration. CGRP did not alter a calcium ionophore A23187-increased cytosolic Ca 2+ concentration in mucosal-type bone marrow-derived mast cells (mBMMCs), but did augment microtubule reorganization in resting and A23187-activated mBMMCs. Furthermore, CGRP alone failed to cause the degranulation of mBMMCs, but CGRP significantly enhanced the degranulation of mBMMCs induced by A23187. Together, these data indicate that CGRPenhanced microtubule reorganization augments IgE-independent/non-antigenic stimuli-induced mucosal mast cell degranulation, thereby contributing to the development of FA.Food allergy (FA) is a serious public health concern that is estimated to affect approximately 5% of children and 3-4% of adults in developed countries (18). The pathogenic mechanisms underlying FA are not fully understood despite the epidemic prevalence and its life-threatening potential, and there is neither a curative drug treatment nor an effective means of prevention (3). Therefore, a deeper understanding of the pathology of FA is needed.Mast cells play a central role as effector and conductor cells in the development of various allergic diseases via the release of various inflammatory mediators, such as proteases, eicosanoids, biogenic amines, cytokines and chemokines (1). High affinity IgE receptor (FcεRI)-mediated mast cell degranulation process can be divided into the following two process as the calcium-independent and microtubule-dependent translocation of granules to the plasma membrane and the calcium-dependent fusion of granules with the plasma membrane for exocytosis (14). Mast cells are classified as mucosal mast cells or connective tissue mast cells. It is well known that mucosal mast cells are morphologically, biochemically and functionally distinct from connective tissue mast cells. We have previously demonstrated that our murine FA model exhibits several features

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Effect Of Cgrp On Mbmmcsmentioning

confidence: 99%

CGRP, a neurotransmitter of enteric sensory neurons, contributes to the development of food allergy due to the augmentation of microtubule reorganization in mucosal mast cells

et al. 2014

Self Cite

View full text Add to dashboard Cite

show abstract

“…In situations of a compromised intestinal barrier, mucosal mast cells are among the first immune cells to release inflammatory mediators and drive mesenteric afferent vagus nerve signaling (Jiang et al 2011). Mast cell activity was shown to be inhibited by the vagal neurotransmitter acetylcholine via the α7nACh receptor (Kageyama-Yahara et al 2008;de Haan et al 2013a). In addition, vagal inhibition of mucosal mast cells was effectuated by lipid-rich enteral nutrition via CCK-1 receptors (de Haan et al 2013a).…”

Section: Nutritional Vagus Stimulation and Intestinal Integritymentioning

confidence: 97%

Nutritional Modulation of Immune Response via Vagus Nerve: Preclinical Studies and Future Perspectives

Haan¹,

Lubbers²,

Luyer³

et al. 2015

Diet and Nutrition in Critical Care

View full text Add to dashboard Cite

“…GTS-21, an ␣7-selective partial agonist, has relatively low efficacy for human ␣7 receptors and produces prolonged desensitization (Papke et al, 2009). In addition to its effects on neuronal ␣7, GTS-21 has also been documented to have ␣7-mediated effects in non-neuronal cells in which no ␣7-mediated ion currents have been detected (Giebelen et al, 2007a,b;Wongtrakool et al, 2007;Kageyama-Yahara et al, 2008). In some cases, ␣7-dependent effects, particularly in non-neuronal cells, have been shown to require downstream events such as modulation of voltage-dependent calcium channels (Ren et al, 2005) or intracellular signal transduction pathways (Marrero et al, 2004;Giebelen et al, 2007a,b).…”

Section: Alpha7 Nachr Inhibition By Novel Antagonists 663mentioning

confidence: 99%

Selective Inhibition of Acetylcholine-Evoked Responses of α7 Neuronal Nicotinic Acetylcholine Receptors by Novel tris- and tetrakis-Azaaromatic Quaternary Ammonium Antagonists

López-Hernández

Thinschmidt

Zheng

et al. 2009

Molecular Pharmacology

View full text Add to dashboard Cite

A family of 20 tris-azaaromatic quaternary ammonium (AQA) compounds were tested for their inhibition of ␣7 nicotinic acetylcholine receptors (nAChRs) expressed in Xenopus laevis oocytes. The potency of inhibitory activity was related to the hydrophobic character of the tris head groups. Two tris-AQA compounds were studied in detail: the highly effective inhibitor 1,3,5-tri-[5-(1-quinolinum)-pent-1-yn-1-yl]-benzene tribromide (tPyQB) and the less potent antagonist 1,3,5,-tri-{5-[1-(2-picolinium)]-pent-1-yn-1-yl}benzene tribromide (tPy2PiB). In addition, we evaluated 1,2,4,5-tetra-{5-[1-(3-benzyl)pyridinium]pent-1-yl}benzene tetrabromide (tkP3BzPB), a tetrakis-AQA with very hydrophobic headgroups. We compared the activity of the AQA compounds to the frequently used ␣7-antagonist methyllycaconitine (MLA). Both tPyQB and tkP3BzPB were selective antagonists of ␣7. However, although inhibition by tPyQB was reversible within 5 min, the recovery time constant for tkP3BzPB inhibition was 26.6 Ϯ 0.8 min, so that the equilibrium inhibition in the prolonged presence of nanomolar concentrations of tkP3BzPB was nearly 100%. The potency, selectivity, and slow reversibility of tkP3BzPB were comparable with or greater than that of MLA. The inhibitory actions of tPyQB, tPy2PiB, and tkP3BzPB were evaluated on the acetylcholine (ACh)-evoked responses of native nAChRs in rat brain slices. The ␣7-mediated responses of hippocampal interneurons were effectively reduced by 1 M tPyQB and tkP3BzPB but not tPy2PiB. In rat medial septum, tkP3BzPB produced a greater inhibition of ACh-evoked responses of cells with fast inward currents (type I) than of cells with predominantly slow kinetics (type II), suggesting that tkP3BzPB can block ␣7 yet preserve the responsiveness of non-␣7 receptors. These agents might be helpful in elucidating complex receptor responses in brain regions with mixed populations of nAChRs.Nicotinic acetylcholine receptors (nAChRs) are distributed throughout the central and peripheral nervous systems (Role and Berg, 1996;Wonnacott, 1997). Nine neuronal ␣ subunits (␣2-␣10) and three neuronal ␤ subunits (␤2-␤4) have thus far been identified and cloned in vertebrate systems. One type of neuronal nAChR is formed by the assembly of ␣ and ␤ subunits, with functional properties depending on both ␣ and ␤ subunits within the receptor complex (Buisson and Bertrand, 2002). In Xenopus laevis oocytes, pairwise combinations of some neuronal ␣ and ␤ subunits form functional receptors. However, the existence of complex subtypes consisting of more than two different subunits has been documented in native brain regions. In addition to the heteromeric recep-

show abstract

IgE-induced degranulation of mucosal mast cells is negatively regulated via nicotinic acetylcholine receptors

Cited by 69 publications

References 26 publications

CGRP, a neurotransmitter of enteric sensory neurons, contributes to the development of food allergy due to the augmentation of microtubule reorganization in mucosal mast cells

CGRP, a neurotransmitter of enteric sensory neurons, contributes to the development of food allergy due to the augmentation of microtubule reorganization in mucosal mast cells

Nutritional Modulation of Immune Response via Vagus Nerve: Preclinical Studies and Future Perspectives

Selective Inhibition of Acetylcholine-Evoked Responses of α7 Neuronal Nicotinic Acetylcholine Receptors by Novel tris- and tetrakis-Azaaromatic Quaternary Ammonium Antagonists

Contact Info

Product

Resources

About