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Source of the elevation Ca2+ evoked by 15-HETE in pulmonary arterial myocytes.

Abstract：

:We have previously reported that 15-hydroxyeicosatetraenoic acid (15-HETE), a metabolite of arachidonic acid by 15-lipoxygenase, causes pulmonary vasoconstriction via increasing the intracellular Ca(2+) concentration ([Ca(2+)]i). However, the multiple sources of Ca(2+) that contribute to Ca(2+) elevation during and after 15-HETE exposure have not been investigated. In the present study, pulmonary arterial ring technique and confocal laser scanning microscope were used to investigate the origin of Ca(2+). 15-HETE (1 microM) elicited an increase in [Ca(2+)]i in pulmonary artery smooth muscle cells in a time-dependent manner under both normal and hypoxic condition. The increases were composed of an initial rapid rise followed by a slow increase in the present of extracellular Ca(2+). The initial rapid phase was attenuated by inositol 1,4,5-triphosphate (IP(3)) receptor antagonist 2-aminoethoxydiphenyl borate (2-APB) and ryanodine receptor-operated Ca(2+) store depletion agent caffeine; the slow increasing phase and the constriction of pulmonary arterial ring were significantly inhibited by voltage-operated Ca(2+) channel blocker nifedipine or transient receptor potential canonical (TRPC) channel blocker La(3+), and almost completely diminished in Ca(2+)-free external solution, suggesting that the initial phase depends on intracellular Ca(2+) store and the second phase relies on extracellular Ca(2+). Interestingly, the effect of caffeine and La(3+) but not nifedipine were diminished in the present of 2-APB. Thus, these results suggest that 15-HETE mobilizes Ca(2+) signaling through: 1) Ca(2+) release immediately from Ca(2+) stores via activation of IP(3) receptor and, subsequently that of ryanodine receptor, 2) the depletion of Ca(2+) through CCE leading to the activation of TRPC, and 3) Ca(2+) entry through L-type Ca(2+) channels.

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Zheng X,Li Q,Tang X,Liang S,Chen L,Zhang S,Wang Z,Guo L,Zhang R,Zhu D

doi

10.1016/j.ejphar.2008.10.028

subject

Has Abstract

pub_date

2008-12-28 00:00:00

pages

16-22

issue

1-3

eissn

0014-2999

issn

1879-0712

pii

S0014-2999(08)01060-1

journal_volume

601

pub_type

杂志文章

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Source of the elevation Ca2+ evoked by 15-HETE in pulmonary arterial myocytes.