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

Jeffrey J. Bowden, Peter Baluk, Peter M. Lefevre, Steven R. Vigna, Donald M. McDonald

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46 Citations (Scopus)

Abstract

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 μm2 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 μg/kg iv). Although both substance P (5 μg/kg iv) and platelet-activating factor (5 μg/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.

Original languageEnglish
Pages (from-to)L404-L413
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume270
Issue number3 14-3
Publication statusPublished - 1 Mar 1996

Keywords

  • endosomes
  • immunohistochemistry
  • neurogenic inflammation
  • plasma leakage
  • postcapillary venules
  • receptor internalization
  • tachykinins
  • vagal stimulation
  • vascular permeability

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