Role for G(12)/G(13) in agonist-induced vascular smooth muscle cell
contraction
Circ Res, 87 (3):
221-7 (August 2000)Gohla, A Schultz, G Offermanns, S Research Support, Non-U.S. Gov't
United states Circulation research Circ Res. 2000 Aug 4;87(3):221-7..Zusammenfassung
Receptor-induced vascular smooth muscle cell contraction is mediated
by dual regulation of myosin light chain (MLC(20)) phosphorylation
through Ca(2+)-dependent stimulation of myosin light chain kinase
and Rho/Rho-kinase-mediated inhibition of myosin phosphatase. Although
myosin light chain kinase regulation is initiated by the coupling
of receptors to G proteins of the G(q) family, G(q) and G(11), it
is not known how receptors regulate the Rho/Rho-kinase-mediated pathway.
In vascular smooth muscle cells, receptor-mediated MLC(20) phosphorylation
and cell contraction was blocked by inhibitors of each of the pathways.
Receptors of various vasocontractors were found to couple to G(q)/G(11)
and G(12)/G(13), and constitutively active forms of G alpha(12) and
G alpha(13) induced a pronounced contraction of vascular smooth muscle
cells that could be blocked by C3 exoenzyme, by inhibition of Rho-kinase,
and by stable analogues of cGMP and cAMP. Receptor-mediated smooth
muscle cell contraction was strongly inhibited by dominant-negative
forms of G alpha(12) and G alpha(13). These data indicate that a
G(12)/G(13)-mediated Rho/Rho-kinase-dependent pathway operates in
smooth muscle cells and that dual regulation of MLC(20) phosphorylation
by vasocontractors is initiated by the dual coupling of their receptors
to G proteins of the G(q) and G(12) families.