Functional Neuroklnin 1 Receptors for Substance P Are Expressed by Human Vascular Endothelium

Edward W. Greeno, Patrick Mantyh, Gregory M. Vercellotti, Charles F. Moldow

Research output: Contribution to journalArticlepeer-review

67 Scopus citations

Abstract

Substance P (SP), a neurotachykinin, is important in a number of inflammatory processes in which the endothelial cell also plays a critical role. SP receptors have previously been identified only on arterial endothelium, and the scant in vitro evidence for direct effects of SP on human endothelium is based on studies using nonarterial cells. To better understand SP's role in inflammation, we sought to identify functional SP receptors on human endothelium in situ and in culture. Autoradiographic ligand binding to human umbilical cord sections demonstrates the presence of SP binding sites with characteristics of the neurokinin 1 (NK-1) receptor (displacement by GTP analogues and the NK-1 specific antagonist CP-96,345) on human umbilical arterial, but not venous, endothelium. In culture, human umbilical venous endothelial cells (HUVECs) and human aortic endothelial cells express low levels of available SP binding sites. However, HUVECs, which are serum starved and refed, undergo a dramatic increase in SP binding. SP binding to starved/refed HUVECs induces a transient increase in intracellular calcium. This calcium flux is dose dependent over appropriate SP concentrations and can be blocked by NK-1 specific antagonists. The proinflammatory effects of SP may be mediated in part through the NK-1 receptor on endothelium.

Original languageEnglish (US)
Pages (from-to)1269-1276
Number of pages8
JournalJournal of Experimental Medicine
Volume177
Issue number5
DOIs
StatePublished - May 1 1993
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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