Angiotensin ii activates the [beta]1 isoform of phospholipase c in
vascular smooth muscle cells.
Schelling, Jeffrey R., Nnenna Nkemere, Martha Konieczkowski, Kathleen
A. Martin and George R. Dubyak.
* Rammelkamp Center for Research and Department of Medicine, Case
Western Reserve University School of Medicine, Cleveland, OH 44109
-1998, ** Department of Physiology and Biophysics, Case Western
Reserve University School of Medicine, Cleveland, OH 44106
APStracts 3:0412C, 1996.
Vascular smooth muscle cells (VSMC) contribute to the pathophysiology
of hypertension through cell growth and contraction, and
phospholipase C (PLC) is a critical effector enzyme in growth factor
and vasoconstrictor signaling. There is indirect evidence that
angiotensin II (ANG II) receptors are linked to PLC[beta] isoform
signaling pathways. However, recent studies suggest that PLC[beta]
isoforms may not be expressed in VSMC. Our data demonstrate that in
human aortic VSMC, PLC[beta]1 and PLC[gamma]1 proteins were detected
by immunoblot analysis, and PLC[beta]1 mRNA was identified by RT-PCR
in rat aortic VSMC. Incubation of permeabilized VSMC with anti
-PLC[beta]1 or anti-Gq[alpha] antibodies inhibited ANG II-dependent
inositol polyphosphate (IP) formation, while anti-PLC[gamma]1
antibodies did not inhibit ANG II-regulated IP formation. Conversely,
anti-PLC[gamma]1 antibodies completely abolished PDGF-dependent IP
generation, whereas anti-PLC[beta]1 antibodies had no effect on PDGF
-induced PLC activation. Inhibition of tyrosine phosphorylation with
genistein or herbimycin A did not diminish ANG II-stimulated IP
formation or Ca2+i transients, thereby confirming that ANG II signals
via a PLC[gamma]1-independent mechanism. In summary, PLC[beta]1 and
PLC[gamma]1 are expressed in human aortic VSMC, and PLC[beta]1 is the
isoform which is critical for ANG II-regulated PLC signaling in these
cells.
Received 29 March 1996; accepted in final form 13 December 1996.
APS Manuscript Number C180-6.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996