Back to Search
Start Over
In vitro activation of murine DRG neurons by CGRP-mediated mucosal mast cell degranulation.
- Source :
-
American journal of physiology. Gastrointestinal and liver physiology [Am J Physiol Gastrointest Liver Physiol] 2004 Jul; Vol. 287 (1), pp. G178-91. Date of Electronic Publication: 2004 Mar 11. - Publication Year :
- 2004
-
Abstract
- Upregulation of CGRP-immunoreactive (IR) primary afferent nerve fibers accompanied by mastocytosis is characteristic for the Schistosoma mansoni-infected murine ileum. These mucosal mast cells (MMC) and CGRP-IR fibers, which originate from dorsal root (DRG) and nodose ganglia, are found in close apposition. We examined interactions between primary cultured MMC and CGRP-IR DRG neurons in vitro by confocal recording of intracellular Ca(2+) concentration ([Ca(2+)](i)). The degranulatory EC(50) for the mast cell secretagogue compound 48/80 (C48/80; 10 microg/ml) and the neuropeptides CGRP (2.10(-8) M) and substance P (SP; 3.10(-8) M) were determined by measurement of extracellular release of the granule chymase, mouse mast cell protease-1. Application of C48/80 (10 microg/ml) and CGRP and SP (both 10(-7) M) to Fluo-4-loaded MMC induced a transient rise in [Ca(2+)](i) after a lag time, indicative of mast cell degranulation and/or secretion. The CGRP response could be completely blocked by pertussis toxin (2 microg/ml), indicating involvement of G(i) proteins. Application of MMC juice, obtained by C48/80 degranulation of MMC, to Fluo-4-loaded DRG neurons induced in all neurons a rise in [Ca(2+)](i), indicative of activation. Degranulation of MMC by C48/80 in culture dishes containing Fluo-4-loaded DRG neurons also caused activation of the DRG neurons. In conclusion, these results demonstrate a bidirectional cross-talk between cultured MMC and CGRP-IR DRG neurons in vitro. This indicates that such a communication may be the functional relevance for the close apposition between MMC and CGRP-IR nerve fibers in vivo.
- Subjects :
- Animals
Body Fluids physiology
Calcitonin Gene-Related Peptide pharmacology
Calcium metabolism
Cells, Cultured
Ganglia, Spinal cytology
Intestinal Mucosa cytology
Intestinal Mucosa metabolism
Intracellular Membranes metabolism
Male
Mast Cells metabolism
Mice
Osmolar Concentration
Substance P pharmacology
p-Methoxy-N-methylphenethylamine pharmacology
Calcitonin Gene-Related Peptide metabolism
Cell Degranulation physiology
Ganglia, Spinal physiology
Intestinal Mucosa physiology
Mast Cells physiology
Neurons physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0193-1857
- Volume :
- 287
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Gastrointestinal and liver physiology
- Publication Type :
- Academic Journal
- Accession number :
- 15016615
- Full Text :
- https://doi.org/10.1152/ajpgi.00528.2003