Title
CGRP1 receptor activation induces piecemeal release of protease-1 from mouse bone marrow-derived mucosal mast cells CGRP1 receptor activation induces piecemeal release of protease-1 from mouse bone marrow-derived mucosal mast cells
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences . Biomedical Sciences
Publication type
article
Publication
Cambridge, Mass. ,
Subject
Biology
Human medicine
Source (journal)
Neurogastroenterology and motility / European Gastrointestinal Motility Society. - Cambridge, Mass., 1994, currens
Volume/pages
23(2011) :2 , p. e57-e68
ISSN
1350-1925
1365-2982
ISI
000286211600003
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
Background  The parasitized or inflamed gastrointestinal mucosa shows an increase in the number of mucosal mast cells (MMC) and the density of extrinsic primary afferent nerve fibers containing the neuropeptide, calcitonin gene-related peptide (CGRP). Currently, the mode of action of CGRP on MMC is unknown. Methods  The effects of CGRP on mouse bone marrow-derived mucosal mast cells (BMMC) were investigated by measurements of intracellular Ca2+ [Ca2+]i and release of mMCP-1. Key Results  Bone marrow-derived mucosal mast cells responded to the application of CGRP with a single transient rise in [Ca2+]i. The proportion of responding cells increased concentration-dependently to a maximum of 19 ± 4% at 10−5 mol L−1 (mean ±SEM; C48/80 100%; EC50 10−8 mol L−1). Preincubation with the CGRP receptor antagonist BIBN4096BS (10−5 mol L−1) completely inhibited BMMC activation by CGRP [range 10−5 to 10−11 mol L−1; analysis of variance (anova)P < 0.001], while preincubation with LaCl3 to block Ca2+ entry did not affect the response (P = 0.18). The presence of the CGRP1 receptor on BMMC was confirmed by simultaneous immunofluorescent detection of RAMP1 or CRLR, the two components of the CGRP1 receptor, and mMCP-1. Application of CGRP for 1 h evoked a concentration-dependent release of mMCP-1 (at EC50 10% of content) but not of β-hexosaminidase and alterations in granular density indicative of piecemeal release. Conclusions & Inferences   We demonstrate that BMMC express functional CGRP1 receptors and that their activation causes mobilization of Ca2+ from intracellular stores and piecemeal release of mMCP-1. These findings support the hypothesis that the CGRP signaling from afferent nerves to MMC in the gastrointestinal wall is receptor-mediated.`
E-info
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