Wang JP, Chen YS, Tsai CR, Huang LJ,
Kuo SC.The blockade of cyclopiazonic acid (CPA) -induced
store-operated Ca2+ entry pathway by YC-1 in neutrophils.
Biochem Pharmacol. 2004 Nov 15;68(10):2053-64.
Department of Education and Research, Taichung Veterans
General Hospital, Taichung 407, Taiwan, Republic of China.
w1994@vghtc.gov.tw
In the presence of external Ca2+, pretreatment of neutrophils
with 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1)
inhibited the cyclopiazonic acid -induced [Ca2+](i) elevation in
a concentration- but not a time-dependent manner, while YC-1 had
no effect on the Ca2+ signals in a Ca2+-free medium. YC-1 failed
to inhibit ATP- and interleukin-8 (IL-8)-induced [Ca2+](i)
changes. Addition of YC-1 after cell activation strongly
inhibited the cyclopiazonic acid (CPA)-induced [Ca2+](i)
changes. In a classical Ca2+ readdition protocol, a similar
extent inhibition of Ca2+ spike by YC-1 introduced either prior
to or after cyclopiazonic acid (CPA) stimulation was obtained.
In rat neutrophils, mRNA for endothelial differentiation gene
(edg)1, edg5, edg6 and edg8, the putative targets for
sphingosine 1-phosphate (S1P), could be detected. However, S1P
was found to have little effect on Ca(2+) signals. YC-1 did not
inhibit but enhanced the sphingosine-induced [Ca2+](i) changes.
Inhibition by YC-1 of cyclopiazonic acid (CPA)-induced [Ca2+](i)
changes was not prevented by 7-nitroindazole and
N-(3-aminomethyl)benzylacetamidine (1400W), two nitric oxide
synthase (NOS) inhibitors, by aristolochic acid, a phospholipase
A(2) inhibitor, or by suspension in a Na(+)-deprived medium.
YC-1 did not affect the mitochondrial membrane potential.
Moreover, YC-1 did not alter [Ca2+](i) changes in response to
ionomycin after cyclopiazonic acid (CPA) and formyl-Met-Leu-Phe
(fMLP) stimulation in a Ca2+-free medium. YC-1 had no effect on
the basal [Ca2+](i) level, the pharmacologically isolated plasma
membrane Ca2+-ATPase activity, and Ba2+ entry into cyclopiazonic
acid (CPA)-activated cells. YC-1 alone resulted in the
accumulation of actin filaments in neutrophils, while
significantly reduced the intensity of actin filament staining
in the subsequent activation with cyclopiazonic acid (CPA).
These results indicate that YC-1 inhibited cyclopiazonic acid
(CPA)-activated store-operated Ca2+ entry (SOCE) probably
through the direct blockade of channel activation and/or the
disruption of the integrity of the actin cytoskeleton necessary
for supporting Ca2+ entry pathway in neutrophils.
PMID: 15476676
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