Thromboxane A2 induces contraction of human prostate smooth muscle by Rho kinase- and calmodulin-dependent mechanisms.
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 3 μM. U46619-induced prostate contraction was significantly inhibited by Y27632 (30 μM) and by W7 (100 μM). 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.
Department of Urology, University of Munich, Munich, Germany.
Frank
F
Strittmatter
Christian
C
Gratzke
Philipp
P
Weinhold
Christian J
CJ
Steib
Anna C
AC
Hartmann
Boris
B
Schlenker
Karl-Erik
KE
Andersson
Petter
P
Hedlund
Christian G
CG
Stief
Martin
M
Hennenberg
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000368:Aged; D000577:Amides / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D011467:Prostate / Q000187:drug effects* / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000819:agonists / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology; D013928:Thromboxane A2 / Q000494:pharmacology*; D013930:Thromboxane-A Synthase / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*
D000577:Amides; D002147:Calmodulin; D004791:Enzyme Inhibitors; D011725:Pyridines; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D013449:Sulfonamides; D014662:Vasoconstrictor Agents; C108830:Y 27632; D013928:Thromboxane A2; C017967:W 7; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D054460:rho-Associated Kinases; D013930:Thromboxane-A Synthase; D002118:Calcium