Substance p (nk1) receptor immunoreactivity on endothelial cells of
the rat tracheal mucosa.
Bowden, Jeffrey J., Peter Baluk, Peter M. Lefevre, Steven R. Vigna,
and Donald M. McDonald.
Cardiovascular Research Institute and Department of Anatomy,
University of California, San Francisco, CA 94143 and Department of
Cell Biology, Duke University Medical Center, Durham, NC 27710
APStracts 2:0191L, 1995.
Substance P released from sensory nerve fibers causes plasma leakage
through an action on neurokinin-1 (NK1 or substance P) receptors.
However, it is unknown whether the leakage results from a direct
action of substance P on endothelial cells. We determined the
distribution of NK1 receptors at sites of plasma leakage in the rat
tracheal mucosa, using NK1 receptor immunoreactive endosomes as
markers of substance P-induced receptor internalization. We found
that immunoreactive endosomes were located in the endothelial cells
of venules and capillaries but not in those of arterioles. Five
minutes after vagal stimulation for 1 min, the number of
immunoreactive endosomes in endothelial cells was increased 5-fold in
postcapillary venules (mean of 17.4 endosomes per 100 [mu]m2 compared
to a baseline value of 3.4), 15-fold in collecting venules (12.1
compared to 0.8), and 4-fold in capillaries (2.5 compared to 0.7). No
endosomes were found in arterioles under either condition. The number
of immunoreactive endosomes in individual vessels corresponded to the
amount of stimulus-induced plasma leakage. Both the receptor
internalization and the plasma leakage were blocked by the selective
NK1 receptor antagonist SR 140333 (100 [mu]g/kg iv). Although both
substance P (5 [mu]g/kg iv) and platelet activating factor (5
[mu]g/kg iv) caused plasma leakage, only substance P induced receptor
internalization. We conclude that substance P, released from sensory
nerve fibers, causes plasma leakage through a direct action on
endothelial cells of venules and that this action is followed by the
internalization of NK1 receptors into endosomes.
Received 3 May 1995; accepted in final form 11 October 1995.
APS Manuscript Number L133-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95