HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 295/4/H1529    most recent 00115.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Xu, M. Articles by Yuan, J. X.-J. Search for Related Content PubMed PubMed Citation Articles by Xu, M. Articles by Yuan, J. X.-J.

p75 neurotrophin receptor regulates agonist-induced pulmonary vasoconstriction

Departments of ¹Medicine and ²Pharmacology, University of California-San Diego, La Jolla, California

Submitted 1 February 2008 ; accepted in final form 29 July 2008

A member of the TNF receptor family, the p75 neurotrophin receptor (p75^NTR) has been previously shown to play a role in the regulation of fibrin deposition in the lung. However, the role of p75^NTR in the regulation of pulmonary vascular tone in the lung is unknown. In the present study, we evaluated the expression of p75^NTR in mouse pulmonary arteries and the putative role of p75^NTR in modulating pulmonary vascular tone and agonist responsiveness using wild-type (WT) and p75^NTR knockout (p75^–/–) mice. Our data indicated that p75^NTR is expressed in both smooth muscle and endothelial cells within the pulmonary vascular wall in WT mice. Pulmonary artery rings from p75^–/– mice exhibited significantly elevated active tension due to endothelin-1-mediated Ca²⁺ influx. Furthermore, the contraction due to capacitative Ca²⁺ entry (CCE) in response to phenylephrine-mediated active depletion of intracellular Ca²⁺ stores was significantly enhanced compared with WT rings. The contraction due to CCE induced by passive store depletion, however, was comparable between WT and p75^–/– rings. Active tension induced by serotonin, U-46619 (a thromboxane A₂ analog), thrombin, 4-aminopyridine (a K⁺ channel blocker), and high extracellular K⁺ in p75^–/– rings was similar to that in WT rings. Deletion of p75^NTR did not alter pulmonary vasodilation to sodium nitroprusside (a nitric oxide donor). These data suggest that intact p75^NTR signaling may play a role in modulating pulmonary vasoconstriction induced by endothelin-1 and by active store depletion.

mouse; pulmonary artery; pharmacology; vasoconstriction; store depletion