Overview
- Asano, T. et al. (1989) Br. J. Pharmacol. 98, 1091.
- Uehata, M. et al. (1997) Nature 389, 990.
- Nagumo, H. et al.(2000) Am. J. Physiol. 278, C57.
- Takayasu, M. et al. (1989) J. Neurosurg. 65, 80.
Alomone Labs HA-1077 inhibits the phosphorylation of myosin light chain (MLC) in C2C12 cells.Cells were grown in fetal calf serum (FCS) to 2 days post-confluence. They were then stimulated with 2% horse serum (HS) or not (FCS) in the presence or absence of 20 µM HA-1077 (#H-220) for the indicated times. Cell proteins were resolved by SDS-PAGE and probed with anti-phospho- MLC.
HA-1077 is a small, cell permeable derivative of isoquinoline which specifically inhibits the small GTPase - Rho by inhibition of its associated kinase-Rho dependent kinase (ROK). This signaling pathway acts as a molecular switch to control cytoskeleton organization in many cell types including smooth muscle.1-3 By inhibition of ROK, HA-1077 decreases the myosin light chain (MLC) phosphorylation induced by Ca2+ due to abrogating Rho-mediated inhibition of MLC dephosphorylation. HA-1077 also inhibits fetal calf serum-induced proliferation and [3H]thymidine incorporation into DNA of growth-arrested VSMC in a dose-dependent manner.4-6
At concentrations higher than 5 µM, it induces disorganization of actin filament structure. This compound was also found to act as a vasodilator and antivasospasm drug which antagonizes the verapamil-insensitive voltage dependent Ca2+ channel and is used clinically for treatment of the cerebral vasospasm after subarachnoid hemorrhage.7-9
