| Project/Area Number |
07672370
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Biological pharmacy
|
|---|
| Research Institution | Department of Pharmacology, Faculty of Pharmaceutical Sciences, University of Shizuoka |
|---|
Principal Investigator |
NAKAYAMA Koichi Department of Pharmacology, Faculty of Pharmaceutical Sciences, University of Shizuoka, Professor and Head, 薬学部・薬理学教室, 教授 (50112769)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
ISHII Kunio Department of Pharmacology, Faculty of Pharmaceutical Sciences, University of Sh, 薬学部, 助教授 (90137993)
|
|---|
| Project Period (FY) |
1995 – 1996
|
| Project Status |
Completed (Fiscal Year 1996)
|
| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1996: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1995: ¥1,700,000 (Direct Cost: ¥1,700,000)
|
|---|
| Keywords | mechano-reception / stretch / myogenic contraction / vascular tissue / tyrosine kinase / protein tyrosyl phosphorylation / adhesion molecule / cellar signal transduction / tyrosine kinase / cerebral artery / myogenic tone / tyrosine kinase inhbitor / genistein / tyrphostin 23 / herbimycin A / intracellular signaling |
|---|
| Research Abstract |
In order to determine whether protein tyrosine kinase mechanisms are involved in pressure-induced contraction, we compared effects of three structurally-unrelated tyrosine kinase inhibitors and orthovanadate, a tyrosine phosphatase inhibitor, on the pressure-induced contraction of the posterior cerebral artery isolated from rats. The change in vessel diameter was continuously measured with a width analyzer. Herbimycin A inhibited the pressure-induced contraction, while it only slightly inhibited contractions produced by potassium chloride or 9,11 dideoxy-11alpha, 9alpha-epoxymethano prostaglandin F2alpha (U46619). Genistein inhibited not only the pressure-induced contraction but also the U46619-induced one. Tyrphostin 23 significantly attenuated contractions in response to three different stimuli, i.e., pressure, potassium chloride, and U46619. Orthovanadate potentiated the pressure-induced contraction. These results suggest that herbimycin A is the most specific and potent inhibitor of the pressure-induced contraction and that a protein tyrosine kinase machanism may play an important role in the genesis of the pressure-induced contraction of the rat cerebral artery.
|
