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Protein kinase mediated upregulation of endothelin A, endothelin B and 5-hydroxytryptamine 1B/1D receptors during organ culture in rat basilar artery.

Hansen-Schwartz, Jacob LU ; Svensson, Carl-Lennart; Xu, Cang-Bao LU and Edvinsson, Lars LU (2002) In British Journal of Pharmacology 137(1). p.118-126
Abstract
1 Organ culture has been shown to upregulate both endothelin (ET) and 5-hydroxytryptamine 1B/1D (5-HT(1B/1D)) receptors in rat cerebral arteries. The purpose of the present study was to investigate the involvement of protein kinases, especially protein kinases C (PKC) and A (PKA) in this process. 2 The effect of inhibiting protein kinases during organ culture with staurosporine (unspecific protein kinase inhitor), RO 31-7549 (specific inhibitor of classical PKC's) and H 89 (specific inhibitor of PKA) was examined using in vitro pharmacological examination of cultured vessel segments with ET-1 (unspecific ET(A) and ET(B) agonist), S6c (specific ET(B) agonist) and 5-CT (5-HT(1) agonist). Levels of mRNA coding for the ET(A), ET(B), 5-HT(1B)... (More)
1 Organ culture has been shown to upregulate both endothelin (ET) and 5-hydroxytryptamine 1B/1D (5-HT(1B/1D)) receptors in rat cerebral arteries. The purpose of the present study was to investigate the involvement of protein kinases, especially protein kinases C (PKC) and A (PKA) in this process. 2 The effect of inhibiting protein kinases during organ culture with staurosporine (unspecific protein kinase inhitor), RO 31-7549 (specific inhibitor of classical PKC's) and H 89 (specific inhibitor of PKA) was examined using in vitro pharmacological examination of cultured vessel segments with ET-1 (unspecific ET(A) and ET(B) agonist), S6c (specific ET(B) agonist) and 5-CT (5-HT(1) agonist). Levels of mRNA coding for the ET(A), ET(B), 5-HT(1B) and 5-HT(1D) receptors were analysed using real-time RT-PCR. 3 Classical PKC's are critically involved in the appearance of the ET(B) receptor; co-culture with RO 31-7549 abolished the contractile response (6.9+/-1.8%) and reduced the ET(B) receptor mRNA by 44+/-4% as compared to the cultured control. Correlation between decreased ET(B) receptor mRNA and abolished contractile function indicates upstream involvement of PKC. 4 Inhibition of PKA generally had an enhancing effect on the induced changes giving rise to a 7-25% increase in E(max) in response to ET-1, S6c and 5-CT as compared to the cultured control. 5 Staurosporine inhibited the culture induced upregulation of the response of both the ET(A) and the 5-HT(1B/1D) receptors, but had no significant effect on the mRNA levels of these receptors. This lack of correlation indicates an additional downstream involvement of protein kinases. British Journal of Pharmacology (2002) 137, 118-126. doi:10.1038/sj.bjp.0704838 (Less)
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Contribution to journal
publication status
published
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in
British Journal of Pharmacology
volume
137
issue
1
pages
118 - 126
publisher
The British Pharmacological Society
external identifiers
  • wos:000177625500013
  • pmid:12183337
  • scopus:0036727204
ISSN
1476-5381
DOI
10.1038/sj.bjp.0704838
language
English
LU publication?
yes
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572bed60-4380-430e-8b61-9ad140b247a9 (old id 109967)
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http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12183337&dopt=Abstract
date added to LUP
2007-06-29 09:19:27
date last changed
2017-08-13 04:15:04
@article{572bed60-4380-430e-8b61-9ad140b247a9,
  abstract     = {1 Organ culture has been shown to upregulate both endothelin (ET) and 5-hydroxytryptamine 1B/1D (5-HT(1B/1D)) receptors in rat cerebral arteries. The purpose of the present study was to investigate the involvement of protein kinases, especially protein kinases C (PKC) and A (PKA) in this process. 2 The effect of inhibiting protein kinases during organ culture with staurosporine (unspecific protein kinase inhitor), RO 31-7549 (specific inhibitor of classical PKC's) and H 89 (specific inhibitor of PKA) was examined using in vitro pharmacological examination of cultured vessel segments with ET-1 (unspecific ET(A) and ET(B) agonist), S6c (specific ET(B) agonist) and 5-CT (5-HT(1) agonist). Levels of mRNA coding for the ET(A), ET(B), 5-HT(1B) and 5-HT(1D) receptors were analysed using real-time RT-PCR. 3 Classical PKC's are critically involved in the appearance of the ET(B) receptor; co-culture with RO 31-7549 abolished the contractile response (6.9+/-1.8%) and reduced the ET(B) receptor mRNA by 44+/-4% as compared to the cultured control. Correlation between decreased ET(B) receptor mRNA and abolished contractile function indicates upstream involvement of PKC. 4 Inhibition of PKA generally had an enhancing effect on the induced changes giving rise to a 7-25% increase in E(max) in response to ET-1, S6c and 5-CT as compared to the cultured control. 5 Staurosporine inhibited the culture induced upregulation of the response of both the ET(A) and the 5-HT(1B/1D) receptors, but had no significant effect on the mRNA levels of these receptors. This lack of correlation indicates an additional downstream involvement of protein kinases. British Journal of Pharmacology (2002) 137, 118-126. doi:10.1038/sj.bjp.0704838},
  author       = {Hansen-Schwartz, Jacob and Svensson, Carl-Lennart and Xu, Cang-Bao and Edvinsson, Lars},
  issn         = {1476-5381},
  language     = {eng},
  number       = {1},
  pages        = {118--126},
  publisher    = {The British Pharmacological Society},
  series       = {British Journal of Pharmacology},
  title        = {Protein kinase mediated upregulation of endothelin A, endothelin B and 5-hydroxytryptamine 1B/1D receptors during organ culture in rat basilar artery.},
  url          = {http://dx.doi.org/10.1038/sj.bjp.0704838},
  volume       = {137},
  year         = {2002},
}