1998 Fiscal Year Final Research Report Summary
Small GTP-Binding Protein and Signaling on Vascular Smooth Muscle Contraction
| Project/Area Number |
09670100
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
General pharmacology
|
|---|
| Research Institution | Nagoya City University |
|---|
Principal Investigator |
KAWABE Mayumi Nagoya City University, Medical School, Research Associate, 医学部, 助手 (90117862)
|
|---|
| Project Period (FY) |
1997 – 1998
|
| Keywords | smooth muscle / Rho / Translocation / Rho kinase / ACh / myosin light chain phosphorylation / Lysophosphatidic acid / Contraction |
|---|
| Research Abstract |
It is well known that signaling on smooth muscle contraction is regulated by level of myosin light chain (MLC) phosphorylation. The level of MLC phosphorylation is determined by the balance of activities of both myosin light chain kinase (MLCK) and myosin light chain phosphatase (MLCP). The activity of MLCK is dependent on Ca^<2+>/ca1modulin, whereas that of MLCP is regulated through Rho/Rho kinase. We studied a role of Rho/Rho kinase in smooth muscle contraction signaling using intact guinea-pig ileal smooth muscle.
1. Lysophosphaticic acid (LPA), an activator of Rho, induced feeble, but sustained contraction in ileal longitudinal smooth muscle and taenia coli, without marked increases in MLC phosphorylation.
2. Rho kinase inhibitor Y-27632 (1 micromol) inhibited LPA-induced contraction almost completely.
3. Y-27632 (10 micromol) slightly inhibited ACh (1 micromol) -induced contraction at 2 min after administration of the agonist. On the other hand, the inhibitor (10 micromol) showed no effects on high K^+ (50 mM) -induced contraction.
4. At 1 or 10 min after the stimulation of ACh, high K^+ solution or LPA, rho protein in thecytosol fraction decreased without significant changes in rho protein contents in detergent-soluble fraction.
These results indicate that contacting agents (LPA, ACh and high K^+) induced translocation of rho protein in intact smooth muscle of ileum. However, the feeble contraction by the Rho activator and the inhibition of their contractions by the specific inhibitor of Rho kinase suggest that the role of Rho/Rho kinase on the contraction of intact guinea-pig ileal smooth muscle is not so much important.
|
