Angiotensin II-induced delayed stimulation of phospholipase C gamma1 requires activation of both phosphatidylinositol 3-kinase gamma and tyrosine kinase in vascular myocytes.
J Cellular Mol Med. 2006-07-01; 10(3): 734-748
DOI: 10.1111/j.1582-4934.2006.tb00433.x
Read on PubMed
1. J Cell Mol Med. 2006 Jul-Sep;10(3):734-48.
Angiotensin II-induced delayed stimulation of phospholipase C gamma1 requires
activation of both phosphatidylinositol 3-kinase gamma and tyrosine kinase in
vascular myocytes.
Rakotoarisoa L(1), Carricaburu V, Leblanc C, Mironneau C, Mironneau J, Macrez N.
Author information:
(1)Laboratoire de Signalisation et Interactions Cellulaires, Université de
Bordeaux, Bordeaux, France.
In vascular smooth muscles, angiotensin II (AII) has been reported to activate
phospholipase C (PLC) and phosphatidylinositol 3-kinase (PI3K). We investigated
the time-dependent effects of AII on both phosphatidylinositol
3,4,5-trisphosphate (PtdInsP3) and inositol phosphates (InsPs) accumulation in
permeabilized microsomes from rat portal vein smooth muscle in comparison with
those of noradrenaline (NA). AII stimulated an early production of PtdInsP3
(within 30 s) followed by a delayed production of InsPs (within 3-5 min), in
contrast to NA which activated only a fast production of InsPs. The use of
pharmacological inhibitors and antibodies raised against the PI3K and PLC
isoforms expressed in portal vein smooth muscle showed that AII specifically
activated PI3Kgamma and that this isoform was involved in the AII-induced
stimulation of InsPs accumulation. NA-induced InsPs accumulation depended on
PLCbeta1 activation whereas AII-induced InsPs accumulation depended on PLCgamma1
activation. AII-induced PLCgamma1 activation required both tyrosine kinase and
PI3Kgamma since genistein and tyrphostin B48 (inhibitors of tyrosine kinase),
LY294002 and wortmannin (inhibitors of PI3K) and anti-PI3Kgamma antibody
abolished AII-induced stimulation of InsPs accumulation. Increased tyrosine
phosphorylation of PLCgamma1 was only detected for long-lasting applications of
AII and was suppressed by genistein. These data indicate that activation of both
PI3Kgamma and tyrosine kinase is a prerequisite for AII-induced stimulation of
PLCgamma1 in vascular smooth muscle and suggest that the sequential activation of
the three enzymes may be responsible for the slow and long-lasting contraction
induced by AII.
DOI: 10.1111/j.1582-4934.2006.tb00433.x
PMCID: PMC3933155
PMID: 16989733 [Indexed for MEDLINE]