P10.01 INVOLVEMENT OF CALCIUM-CALMODULIN DEPENDENT PROTEIN KINASE II ON ENDOTHELIN RECEPTOR EXPRESSION IN CEREBRAL ARTERIES OF RAT

DOI

10.1016/j.artres.2009.10.132How to use a DOI?

Abstract

Background. Experimental cerebral ischemia and organ culture of cerebral arteries result in enhanced expression of endothelin ET_B 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; ET_A and ET_B receptor agonist) and sarafotoxin 6c (S6c; ET_B receptor agonist) were studied using a sensitive myograph. The mRNA levels of ET_A and ET_B 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 ET_B receptor were increased during organ culture but not for ET_A 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.

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TY  - JOUR
AU  - R. Waldsee
AU  - H. Ahnstedt
AU  - S. Eftekhari
AU  - L. Edvinsson
PY  - 2009
DA  - 2009/12/03
TI  - P10.01 INVOLVEMENT OF CALCIUM-CALMODULIN DEPENDENT PROTEIN KINASE II ON ENDOTHELIN RECEPTOR EXPRESSION IN CEREBRAL ARTERIES OF RAT
JO  - Artery Research
SP  - 191
EP  - 191
VL  - 3
IS  - 4
SN  - 1876-4401
UR  - https://doi.org/10.1016/j.artres.2009.10.132
DO  - 10.1016/j.artres.2009.10.132
ID  - Waldsee2009
ER  -