Substance P (NK1) receptor immunoreactivity on endothelial cells of the rat tracheal mucosa.


Journal Article

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/100 micron2 compared with a baseline value of 3.4), 15-fold in collecting venules (12.1 compared with 0.8), and 4-fold in capillaries (2.5 compared with 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 microgram/kg iv). Although both substance P (5 microgram/kg iv) and platelet-activating factor (5 microgram/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.

Full Text

Duke Authors

Cited Authors

  • Bowden, JJ; Baluk, P; Lefevre, PM; Vigna, SR; McDonald, DM

Published Date

  • March 1996

Published In

Volume / Issue

  • 270 / 3 Pt 1

Start / End Page

  • L404 - L414

PubMed ID

  • 8638733

Pubmed Central ID

  • 8638733

International Standard Serial Number (ISSN)

  • 0002-9513

Digital Object Identifier (DOI)

  • 10.1152/ajplung.1996.270.3.L404


  • eng

Conference Location

  • United States