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(Received for publication, June 21, 1994; and in revised form, October 25, 1994) In non-differentiated NG108-15 cells, both angiotensin II
(Ang II) (100 nM) and CGP 42112 (100 nM) decreased
the T-type calcium current amplitude by 24 ± 2% and 21 ±
3%, respectively. cGMP is not a mediator of the Ang II effect, since
loading of cells with 50 µM cGMP did not prevent the
inhibitory effects of Ang II. The effects of Ang II involves a
non-identified GTPase activity since incubation with GDP
Volume 270,
Number 4,
Issue of January 27, 1995 pp. 1670-1674
©1995 by The American Society for Biochemistry and Molecular Biology, Inc.
Receptor Inhibition of the
T-Type Calcium Current in Non-differentiated NG108
15 Cells
S (3
mM) completely reversed the inhibitory effect of Ang II while
GTPS mimicked its effect. However, Ang II binding was not affected
by GTP
S, and the effect of Ang II was not modified in pertussis
toxin-treated cells. The inhibitory effect of Ang II on the T-type
Ca
current involves a phosphotyrosine phosphatase
activity since sodium orthovanadate prevented the effects of Ang II,
although microcystin-LR, a selective Ser/Thr phosphatase 1 and 2A
inhibitor, did not modify the effect of Ang II. These results provide
the first evidence of a modulation of membrane conductance by Ang II
through the AT
receptor and demonstrate the involvement of
a phosphotyrosine phosphatase and a G protein in the AT transduction mechanism in NG108-15 cells. Moreover, our
data suggest that phosphotyrosine phosphatase activation is proximal to
receptor occupation, since sodium orthovanadate inhibits both GTPase
activity and T-type current blockage induced by Ang II or CGP 42112,
while GTPS inhibition of the T-type calcium current is not
impaired.
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