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Involvement of calcium-calmodulin-dependent protein kinase II in endothelin receptor expression in rat cerebral arteries

Waldsee, Roya LU ; Ahnstedt, Hilda LU ; Eftekhari, Sajedeh LU and Edvinsson, Lars LU (2010) In American Journal of Physiology: Heart and Circulatory Physiology 298(3). p.823-832
Abstract
Waldsee R, Ahnstedt H, Eftekhari S, Edvinsson L. Involvement of calcium-calmodulin-dependent protein kinase II in endothelin receptor expression in rat cerebral arteries. Am J Physiol Heart Circ Physiol 298: H823-H832, 2010. First published December 11, 2009; doi:10.1152/ajpheart.00759.2009.-Experimental cerebral ischemia and organ culture of cerebral arteries result in the enhanced expression of endothelin ETB receptors in smooth muscle cells via increased transcription. The present study was designed to evaluate the involvement of calcium-calmodulin-dependent protein kinase (CAMK) in the transcriptional expression of endothelin receptors after organ culture. Rat basilar arteries were incubated for 24 h with or without the CAMK inhibitor... (More)
Waldsee R, Ahnstedt H, Eftekhari S, Edvinsson L. Involvement of calcium-calmodulin-dependent protein kinase II in endothelin receptor expression in rat cerebral arteries. Am J Physiol Heart Circ Physiol 298: H823-H832, 2010. First published December 11, 2009; doi:10.1152/ajpheart.00759.2009.-Experimental cerebral ischemia and organ culture of cerebral arteries result in the enhanced expression of endothelin ETB receptors in smooth muscle cells via increased transcription. The present study was designed to evaluate the involvement of calcium-calmodulin-dependent protein kinase (CAMK) in the transcriptional expression of endothelin receptors after organ culture. Rat basilar arteries were incubated for 24 h with or without the CAMK inhibitor KN93 or 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 the ETA and ETB receptors and CAMKII were determined by real-time PCR, and their protein levels were evaluated by immunohistochemistry and Western blot. The mRNA levels of CAMKII and the ETB receptor increased during organ culture, but there was no change in the expression of the ETA receptor. This effect was abolished by coincubation with KN93 or U0126. In functional studies, both inhibitors attenuated the S6c-induced contraction. Incubating the arteries with KN93, but not U0126, decreased the amount of phosphorylated CAMKII. The inhibitors had no effect on the levels of myosin light chain during organ culture, as measured by Western blot. CAMKII is involved in the upregulation of the endothelin ETB receptor and interacts with the ERK1/2 pathway to enhance receptor expression. CAMKII has no effect on the contractile apparatus in rat cerebral arteries. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
extracellular signal-regulated kinase 1/2, organ culture
in
American Journal of Physiology: Heart and Circulatory Physiology
volume
298
issue
3
pages
823 - 832
publisher
American Physiological Society
external identifiers
  • wos:000274931500012
  • scopus:77749291929
ISSN
1522-1539
DOI
10.1152/ajpheart.00759.2009
language
English
LU publication?
yes
id
b42817b4-2c39-4ee4-a8c5-773623864224 (old id 1568416)
date added to LUP
2010-03-23 13:09:26
date last changed
2018-05-29 11:09:27
@article{b42817b4-2c39-4ee4-a8c5-773623864224,
  abstract     = {Waldsee R, Ahnstedt H, Eftekhari S, Edvinsson L. Involvement of calcium-calmodulin-dependent protein kinase II in endothelin receptor expression in rat cerebral arteries. Am J Physiol Heart Circ Physiol 298: H823-H832, 2010. First published December 11, 2009; doi:10.1152/ajpheart.00759.2009.-Experimental cerebral ischemia and organ culture of cerebral arteries result in the enhanced expression of endothelin ETB receptors in smooth muscle cells via increased transcription. The present study was designed to evaluate the involvement of calcium-calmodulin-dependent protein kinase (CAMK) in the transcriptional expression of endothelin receptors after organ culture. Rat basilar arteries were incubated for 24 h with or without the CAMK inhibitor KN93 or 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 the ETA and ETB receptors and CAMKII were determined by real-time PCR, and their protein levels were evaluated by immunohistochemistry and Western blot. The mRNA levels of CAMKII and the ETB receptor increased during organ culture, but there was no change in the expression of the ETA receptor. This effect was abolished by coincubation with KN93 or U0126. In functional studies, both inhibitors attenuated the S6c-induced contraction. Incubating the arteries with KN93, but not U0126, decreased the amount of phosphorylated CAMKII. The inhibitors had no effect on the levels of myosin light chain during organ culture, as measured by Western blot. CAMKII is involved in the upregulation of the endothelin ETB receptor and interacts with the ERK1/2 pathway to enhance receptor expression. CAMKII has no effect on the contractile apparatus in rat cerebral arteries.},
  author       = {Waldsee, Roya and Ahnstedt, Hilda and Eftekhari, Sajedeh and Edvinsson, Lars},
  issn         = {1522-1539},
  keyword      = {extracellular signal-regulated kinase 1/2,organ culture},
  language     = {eng},
  number       = {3},
  pages        = {823--832},
  publisher    = {American Physiological Society},
  series       = {American Journal of Physiology: Heart and Circulatory Physiology},
  title        = {Involvement of calcium-calmodulin-dependent protein kinase II in endothelin receptor expression in rat cerebral arteries},
  url          = {http://dx.doi.org/10.1152/ajpheart.00759.2009},
  volume       = {298},
  year         = {2010},
}