主催: The Japanese Pharmacological Society, The Japanese Society of Clinical Pharmacology
会議名: WCP2018 (18th World Congress of Basic and Clinical Pharmacology)
開催地: Kyoto
開催日: 2018/07/01 - 2018/07/06
Bradykinin (BK) is an inflammatory agent that could be involved in causing ureter contraction during stone passage. Rho-Kinase play a key role in the control of the electro- and pharmaco-mechanical coupling in the rat ureter via modulation of calcium influx through L-type voltage-gated calcium channels
and modulation of MLCP activity (Borysova et al., 2011). Moreover, the level of Rho- kinases have been substantially increased in the obstructed rabbit ureter, and the contractile responses induced by various factors were effectively inhibited by the selective blocker of Rho-kinase (Y-27632) (Turna et al., 2007).
Measurement of the force of contractions together with confocal imaging were done after loading strips of the rat ureter with calcium indicator.
Inhibition of Rho-kinase by Y-27632 (10micromolar) in the presence of Nifedipine or calcium free solution had no effect on BK-induced calcium transient, but strongly reduced contractile response. In the presence of Nifedipine, the amplitude of both phasic and tonic components of BK-induced force were reduced by Y-27632 from 63.3+4.7% to 29.5+2.7% and from 22.3+2.7% to 7.1+0.5% (n=16) respectively and in calcium free solution from 58.5+5.3% to 30.9+4.1 (n=15).
Besides, the mean duration at 50% of the peak amplitude of BK-Induced phasic contraction in calcium free solution reduced from 14.1+0.7s to 5.4+0.7s.
The data obtained suggest that there is a substantial inhibition of the in situ MLCP activity by BK in the rat ureteric smooth muscle, via Rho-kinase activation. Inhibition of Rho-kinase has a dramatic effect on the balance of MLCK and MLCP, so that an increase in the activity of MLCP results in antagonizing contractile response induced by BK. Since, BK is an inflammatory factor and contribute to pain caused by ureter obstruction. One could suggest that Rho-kinase inhibitors might be considered as potential pharmacological tools for facilitation of kidney stone passage and prevention of renal colic pain and kidney damage.
Borysova,L., Shabir,S., Burdyga,T.2011. The importance of Rho-asssociated kinase induced calcium sensitization as a component of electromechanical and phrmacmechanical coupling in rat ureter. cell calcium.
Turna,B., Cinar,M., Canada, A. 2007. Role of Rho kinase in contractions of ureter from rabbits with unilateral obstruction. BJU international.
