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  3. Medizin - Open Access LMU - Teil 20/22 Podcast
  4. The cAMP effector EPAC activates Elk1 transcription factor in prostate smooth muscle, and is a minor regulator of alpha 1-adrenergic contraction
Background: Prostate smooth muscle tone is regulated by alpha
1-adrenoceptor-induced contraction and cAMP-mediated relaxation.
EPAC is an effector of cAMP, being involved in smooth muscle
relaxation and cell cycle control outside the lower urinary tract.
Here, we investigated the expression and function of EPAC in human
prostate tissues from patients undergoing radical prostatectomy.
Results: mRNA and protein expression of EPAC was detected in all
prostate tissues by RT-PCR and Western blot analysis.
Immunoreactivity was observed in stromal cells, and colocalized
with immunofluorescence for a-smooth muscle actin and calponin.
Under normal conditions, noradrenaline-or phenylephrine-induced
contraction of prostate strips in the organ bath was not affected
by the EPAC activator pCPT (SP-8-pCPT-2'-O-Me-cAMPS.NA) (30 mu M).
However, when the cyclooxygenase inhibitor indomethacin (50 mu M)
was added, EPAC activators pCPT and OME (8-CPT-2'-O-Me-cAMP.Na) (30
mu M) significantly reduced contractions by low concentrations of
phenylephrine. These effects were not observed on
noradrenaline-induced contraction. OME and pCPT caused
phosphorylation of the transcription factor Elk1 in prostate
tissues. Elk1 activation was confirmed by EMSA (electrophoretic
mobility shift assay), where OME and pCPT incresed Elk1 binding to
a specific DNA probe. Conclusions: EPAC activation may reduce alpha
1-adrenergic prostate contraction in the human prostate, although
this effect is masked by cyclooxygenases and beta-adrenoceptors. A
main EPAC function in the human prostate may be the regulation of
the transcription factor Elk1.

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