Direct observation of substance P-induced internalization of neurokinin 1 (NK1) receptors at sites of inflammation

Jeffrey J. Bowden, Adella M. Garland, Peter Baluk, Peter Lefevre, Eileen F. Grady, Steven R. Vigna, Nigel W. Bunnett, Donald M. McDonald

Research output: Contribution to journalArticle

Abstract

Substance P (SP) can cause plasma leakage at sites of inflammation by binding to neurokinin type 1 (NK1) receptors on the surface of endothelial cells. Internalization after ligand binding could reduce the number of NK1 receptors on the cell surface and thus participate in the desensitization and resensitization of the inflammatory response to SP. By using an antibody to the receptor, we directly observed SP-induced internalization of NK1 receptors into endosomes in endothelial cells of postcapillary venules in the rat tracheal mucosa. In the absence of SP, an average of 15 immunoreactive endosomes were present per endothelial cell. After an intravenous injection of SP, the number of immunoreactive endosomes peaked at 107 per cell at 3 min and gradually returned to the baseline by 120 min. In parallel experiments we observed that when cultured cells transfected with the NK1 receptor were exposed to rhodamine-SP and an antibody to an extracellular Flag epitope of the NK1 receptor, the SP was internalized with the receptor antibody. Both in the cultured cells and in the endothelial cells of intact animals, the prompt SP-induced internalization was accompanied by rapid, long-lasting desensitization to SP. These studies suggest that internalization of NK1 receptors by endothelial cells may be one of the mechanisms that limit the amount of plasma leakage at sites of inflammation.

Original languageEnglish (US)
Pages (from-to)8964-8968
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number19
DOIs
StatePublished - Sep 13 1994

Keywords

  • desensitization
  • endosomes
  • receptor-mediated endocytosis
  • respiratory tract
  • tachyphylaxis

ASJC Scopus subject areas

  • General

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