| Autor: |
R. Waldsee, H. Ahnstedt, S. Eftekhari, L. Edvinsson |
| Jazyk: |
angličtina |
| Rok vydání: |
2009 |
| Předmět: |
|
| Zdroj: |
Artery Research, Vol 3, Iss 4 (2009) |
| Druh dokumentu: |
article |
| ISSN: |
1876-4401 |
| DOI: |
10.1016/j.artres.2009.10.132 |
| Popis: |
Background. Experimental cerebral ischemia and organ culture of cerebral arteries result in enhanced expression of endothelin ETB receptors in smooth muscle cells. The present study was designed to evaluate the involvement of calcium-calmodulin dependent protein kinase (CAMK) on the expression of endothelin receptors. Methods. Rat basilar arteries were incubated for 24hours with and without the CAMK inhibitor, KN93, or the ERK1/2 inhibitor, U0126. The contractile responses to endothelin-1 (ET-1; ETA and ETB receptor agonist) and sarafotoxin 6c (S6c; ETB receptor agonist) were studied using a sensitive myograph. The mRNA levels of ETA and ETB receptors, and of CAMKII were determined with real-time polymerase chain reaction (PCR) while the protein level was evaluated by immunohistochemistry and western blot. Results. The mRNA levels of CAMKII and of the ETB receptor were increased during organ culture but not for ETA receptor. This effect was abolished by co-incubation with KN93 or U0126. In functional studies, both inhibitors attenuated the S6c and potassium induced contractions, and KN93 decreased the ET-1 induced response. This was confirmed at the protein level by immunohistochemistry where the endothelin receptors were found co-localised with CAMKII. Phosphorylated extracellular signal-regulated kinase p-ERK1/2 and CAMKII was measured by immunohistochemistry and western blot. Incubation of arteries with KN93 decreased the protein levels of p-ERK1/2 and CAMKII while U0126 has no effect on CAMKII. Conclusion. Our results show that the CAMK II is involved in the endothelin receptor regulation and interacts with the MEK/ERK1/2 pathway, resulting in enhanced receptors expression in rat cerebral arteries. |
| Databáze: |
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| Externí odkaz: |
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