Substance p enhances electrical field stimulation-induced mast cell
degranulation in rat trachea.
Hua, Xiao-Ying, Steven M. Back, and Elizabeth K. Tam.
Departments of Anesthesiology and Medicine, University of
California, San Diego and San Diego Veterans Administration Medical
Center
APStracts 3:0016L, 1996.
We previously demonstrated in an ex vivo rat tracheal model that
chymotryptic activity is an index of mast cell degranulation, and
that substance P (SP) and electrical field stimulation (EFS)
synergistically degranulate mucosal and connective tissue mast cells.
In the current study we found that the facilitatory effect of SP was
apparent at concentrations as low as 10-9 M. This effect was mimicked
by neurokinin A 10-7 M or by capsaicin 10-6 M, and was blocked by the
NK1 receptor antagonist CP 96,345. SP+EFS-induced mast cell secretion
was significantly attenuated by tetrodotoxin 10-6 M. The response was
also attenuated in tracheas from rats whose sensory nerves had been
depleted by systemic pre-treatment with capsaicin or whose
sympathetic nerves had been depleted by systemic pre-treatment with
6-hydroxydopamine. Atropine 10-6 M or indomethacin 10-5 M also
attenuated SP+EFS-induced mast cell secretion. Our findings suggest
the importance of a sensitizing, rather than a direct stimulating
effect of SP on mast cell degranulation. SP may increase the
sensitivity of mast cells to EFS-discharged mediators or facilitate
the release of mast cell-stimulating mediators from autonomic nerves.
Received 31 July 1995; accepted in final form 5 January 1996.
APS Manuscript Number L237-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 29 January 96