Details

Autor(en) / Beteiligte

• Büyükafşar, Kansu
• Levent, Adnan
• Ark, Mustafa

Titel

Expression of Rho‐kinase and its functional role in the contractile activity of the mouse vas deferens

Ist Teil von

• British journal of pharmacology, 2003-10, Vol.140 (4), p.743-749

Ort / Verlag

Oxford, UK: Blackwell Publishing Ltd

Erscheinungsjahr

2003

Quelle

Elektronische Zeitschriftenbibliothek (Open access)

Beschreibungen/Notizen

• The effects of two Rho‐kinase inhibitors, Y‐27632 and fasudil, were investigated on the contractions produced by electrical field stimulation (EFS, 40 V, 1 mS, 2, 4, 8 and 16 Hz, for 20 s), KCl (30 – 60 mM), phenylephrine (Phe) (10−5 – 10−4 M), adenosine‐3′, 5′‐triphosphate (ATP) (10−4 – 10−3 M) and α,β‐methylene ATP (10−5 M). EFS produced frequency‐dependent reproducible contractile activity, which was almost abolished by guanethidine (10−5 M, for 1 h). This contraction consisted of two components (a phasic initial contraction followed by a tonic one), and it was inhibited by Y‐27632 and fasudil (both at 10−5 M). However, these inhibitors had no effect on resting tension of the tissue. Contractions elicited by KCl (30 – 60 mM) were insensitive to guanethidine (10−5 M, for 1 h), but suppressed by Y‐27632 (10−5 M) and fasudil (10−5 M). In addition, the contractions induced by Phe (an α1‐adrenoceptor agonist) and ATP (a purinergic agent) were inhibited significantly by Y‐27632 (10−5 M). Phasic contractions evoked by the selective P2X purinoceptor agonist α,β‐methylene ATP were also suppressed by Y‐27632 (10−5 M). Western blot analysis revealed that the mouse vas deferens expresses Rho‐kinase (ROKα, ROCK‐2 isoform) protein with a molecular weight of approximately 160 kDa. As a positive control, the presence of this protein was also shown in homogenates of smooth muscle from the rat mesenteric artery. In conclusion, Rho‐kinase protein is expressed in the mouse vas deferens, and it mediates neurogenic contractile activity as well as the contractions induced by KCl, Phe, ATP and α,β‐methylene ATP. Owing to the suppressive effects of Rho‐kinase inhibitors on the contractile activity of the vas deferens, the possibility that these compounds might impair ejaculation must be taken into account when considering them as potential agents in the treatment of erectile dysfunction. British Journal of Pharmacology (2003) 140, 743–749. doi:10.1038/sj.bjp.0705479