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Thromboxane A(2) induces contraction of human prostate smooth muscle by Rho kinase- and calmodulin-dependent mechanisms.

Strittmatter, Frank; Gratzke, Christian; Weinhold, Philipp; Steib, Christian J; Hartmann, Anna C; Schlenker, Boris; Andersson, Karl-Erik LU ; Hedlund, Petter LU ; Stief, Christian G and Hennenberg, Martin (2011) In European Journal of Pharmacology Dec. p.650-655
Abstract
Thromboxane A(2) (TXA(2)) induces contraction in different smooth muscle types via its receptor (TXA(2) receptor). However, any motoric role of TXA(2) in prostate smooth muscle tone has not been studied to date. Here, we investigated whether TXA(2) induces contraction of human prostate tissue. After ethical approval, prostate tissue was obtained from 47 patients undergoing radical prostatectomy. Effects of the TXA(2) analogue U46619 ((5Z)-7-[(1R,4S,5S,6R)-6-[(1E,3S)-3-hydroxy-1-octenyl]-2-oxabicyclo[2.2.1]hept-5-yl]-5-heptonic acid) in isolated human prostate strips were studied in organ bath experiments with or without the Rho kinase inhibitor, Y27632 (trans-4-[(1R)-1-aminoethyl]-N-4-pyridinylcyclohexanecarboxamide dihydrochloride), or... (More)
Thromboxane A(2) (TXA(2)) induces contraction in different smooth muscle types via its receptor (TXA(2) receptor). However, any motoric role of TXA(2) in prostate smooth muscle tone has not been studied to date. Here, we investigated whether TXA(2) induces contraction of human prostate tissue. After ethical approval, prostate tissue was obtained from 47 patients undergoing radical prostatectomy. Effects of the TXA(2) analogue U46619 ((5Z)-7-[(1R,4S,5S,6R)-6-[(1E,3S)-3-hydroxy-1-octenyl]-2-oxabicyclo[2.2.1]hept-5-yl]-5-heptonic acid) in isolated human prostate strips were studied in organ bath experiments with or without the Rho kinase inhibitor, Y27632 (trans-4-[(1R)-1-aminoethyl]-N-4-pyridinylcyclohexanecarboxamide dihydrochloride), or the calmodulin antagonist W7 (N-(6-aminohexyl)-5-chloro-1-naphtalenesulfonamide hydrochloride). Expression of TXA(2) synthase and TXA(2) receptors were examined by Western blot analysis and immunohistochemistry. Endogenous TXA(2) was quantified by enzyme immunoassay. U46619 induced concentration-dependent contractions of human prostate strips, with a maximum contraction at 3μM. U46619-induced prostate contraction was significantly inhibited by Y27632 (30μM) and by W7 (100μM). TXA(2) synthase and TXA(2) receptors were detected by Western blot analysis. Immunohistochemical stainings showed that expression of TXA(2) synthase in prostate tissue was located to glandular cells, while prostate TXA(2) receptors were located to smooth muscle and glandular cells. The stable TXA(2) metabolite TXB(2) was detected by enzyme immunoassay in the prostate. TXA(2) induces contraction of isolated human prostate tissue by TXA(2) receptor activation. Prostate smooth muscle TXA(2) receptors are coupled to Rho kinase and Ca(2+)-dependent mechanisms. The distribution of TXA(2) synthase and TXA(2) receptors in the human prostate suggests TXA(2)-mediated paracrine epithelial-stromal interactions. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
European Journal of Pharmacology
volume
Dec
pages
650 - 655
publisher
Elsevier
external identifiers
  • wos:000290553600021
  • pmid:21044618
  • scopus:78651082265
ISSN
1879-0712
DOI
10.1016/j.ejphar.2010.10.052
language
English
LU publication?
yes
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cfec95d0-5eec-4ffd-8bd5-72ded03fb45b (old id 1732377)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21044618?dopt=Abstract
date added to LUP
2010-12-01 10:18:34
date last changed
2017-05-07 04:28:48
@article{cfec95d0-5eec-4ffd-8bd5-72ded03fb45b,
  abstract     = {Thromboxane A(2) (TXA(2)) induces contraction in different smooth muscle types via its receptor (TXA(2) receptor). However, any motoric role of TXA(2) in prostate smooth muscle tone has not been studied to date. Here, we investigated whether TXA(2) induces contraction of human prostate tissue. After ethical approval, prostate tissue was obtained from 47 patients undergoing radical prostatectomy. Effects of the TXA(2) analogue U46619 ((5Z)-7-[(1R,4S,5S,6R)-6-[(1E,3S)-3-hydroxy-1-octenyl]-2-oxabicyclo[2.2.1]hept-5-yl]-5-heptonic acid) in isolated human prostate strips were studied in organ bath experiments with or without the Rho kinase inhibitor, Y27632 (trans-4-[(1R)-1-aminoethyl]-N-4-pyridinylcyclohexanecarboxamide dihydrochloride), or the calmodulin antagonist W7 (N-(6-aminohexyl)-5-chloro-1-naphtalenesulfonamide hydrochloride). Expression of TXA(2) synthase and TXA(2) receptors were examined by Western blot analysis and immunohistochemistry. Endogenous TXA(2) was quantified by enzyme immunoassay. U46619 induced concentration-dependent contractions of human prostate strips, with a maximum contraction at 3μM. U46619-induced prostate contraction was significantly inhibited by Y27632 (30μM) and by W7 (100μM). TXA(2) synthase and TXA(2) receptors were detected by Western blot analysis. Immunohistochemical stainings showed that expression of TXA(2) synthase in prostate tissue was located to glandular cells, while prostate TXA(2) receptors were located to smooth muscle and glandular cells. The stable TXA(2) metabolite TXB(2) was detected by enzyme immunoassay in the prostate. TXA(2) induces contraction of isolated human prostate tissue by TXA(2) receptor activation. Prostate smooth muscle TXA(2) receptors are coupled to Rho kinase and Ca(2+)-dependent mechanisms. The distribution of TXA(2) synthase and TXA(2) receptors in the human prostate suggests TXA(2)-mediated paracrine epithelial-stromal interactions.},
  author       = {Strittmatter, Frank and Gratzke, Christian and Weinhold, Philipp and Steib, Christian J and Hartmann, Anna C and Schlenker, Boris and Andersson, Karl-Erik and Hedlund, Petter and Stief, Christian G and Hennenberg, Martin},
  issn         = {1879-0712},
  language     = {eng},
  pages        = {650--655},
  publisher    = {Elsevier},
  series       = {European Journal of Pharmacology},
  title        = {Thromboxane A(2) induces contraction of human prostate smooth muscle by Rho kinase- and calmodulin-dependent mechanisms.},
  url          = {http://dx.doi.org/10.1016/j.ejphar.2010.10.052},
  volume       = {Dec},
  year         = {2011},
}