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Y\u201027632 and HA 1077 caused a concentration\u2010dependent inhibition and complete relaxation (IC<jats:sub>50<\/jats:sub>, 1.08 and 1.75\u2003<jats:italic>\u03bc<\/jats:italic><jats:sc>m<\/jats:sc> respectively). The Ca<jats:sup>2+<\/jats:sup>\u2010free contraction was reduced by wortmannin (10\u2003<jats:italic>\u03bc<\/jats:italic><jats:sc>m<\/jats:sc>) or ML\u20109 (10\u2003<jats:italic>\u03bc<\/jats:italic><jats:sc>m<\/jats:sc>) but not by inhibitors of diacylglycerol metabolism, 3\u2010[2\u2010[4[<jats:italic>bis<\/jats:italic>(4\u2010Fluoropheny)methylene]\u20101\u2010piperidinyl]\u20102,3\u2010dihydro\u20102\u2010thioxi\u20104(H)\u2010quinazolinone (R59949) (10\u2003<jats:italic>\u03bc<\/jats:italic><jats:sc>m<\/jats:sc>) or 1,6\u2010<jats:italic>bis<\/jats:italic>(cyclohexyloximinocarbonylamino)hexane (RHC\u201080267) (10\u2003<jats:italic>\u03bc<\/jats:italic><jats:sc>m<\/jats:sc>) or by the phospholipase A<jats:sub>2<\/jats:sub> (PLA<jats:sub>2<\/jats:sub>) inhibitor, quinacrine (up to 100\u2003<jats:italic>\u03bc<\/jats:italic><jats:sc>m<\/jats:sc>) or tyrosine kinase inhibitor, genistein (30\u2003<jats:italic>\u03bc<\/jats:italic><jats:sc>m<\/jats:sc>).<\/jats:p><jats:p> <jats:bold>3<\/jats:bold>\u2003In the presence of Ca<jats:sup>2+<\/jats:sup> (2.5\u2003m<jats:sc>m<\/jats:sc>), noradrenaline (100\u2003<jats:italic>\u03bc<\/jats:italic><jats:sc>m<\/jats:sc>) evoked rhythmic activity and biphasic tonic contractions. Y\u201027632 (1\u201310\u2003<jats:italic>\u03bc<\/jats:italic><jats:sc>m<\/jats:sc>) or HA 1077 (1\u201310\u2003<jats:italic>\u03bc<\/jats:italic><jats:sc>m<\/jats:sc>) reduced the amplitude of rhythmic activity and tonic contractions. ML\u20109 (10\u2003<jats:italic>\u03bc<\/jats:italic><jats:sc>m<\/jats:sc>) attenuated the occurrence of rhythmic activity and modestly reduced the tonic contractions. ML\u20109 (10\u2003<jats:italic>\u03bc<\/jats:italic><jats:sc>m<\/jats:sc>) combined with Y\u201027632 (10\u2003<jats:italic>\u03bc<\/jats:italic><jats:sc>m<\/jats:sc>) significantly reduced the tonic contractions. ML\u20109 (30\u2003<jats:italic>\u03bc<\/jats:italic><jats:sc>m<\/jats:sc>) alone (or combined with Y\u201027632 10\u2003<jats:italic>\u03bc<\/jats:italic><jats:sc>m<\/jats:sc>) suppressed the rhythmic activity and substantially reduced (or abolished) the tonic contractions.<\/jats:p><jats:p> <jats:bold>4<\/jats:bold>\u2003Contractions evoked by high [K<jats:sup>+<\/jats:sup>]<jats:sub>o<\/jats:sub> (120\u2003m<jats:sc>m<\/jats:sc>) or <jats:italic>\u03b1<\/jats:italic>,<jats:italic>\u03b2<\/jats:italic>\u2010methylene ATP (10\u2003<jats:italic>\u03bc<\/jats:italic><jats:sc>m<\/jats:sc>) were reduced significantly by Y\u201027632 (1\u20133\u2003<jats:italic>\u03bc<\/jats:italic><jats:sc>m<\/jats:sc>) indicating that the Rho kinase signalling pathway is activated by direct tissue depolarization or by stimulation of ligand\u2010gated P<jats:sub>2X<\/jats:sub> purinoceptors.<\/jats:p><jats:p> <jats:bold>5<\/jats:bold>\u2003Collectively, these results indicate that Ca<jats:sup>2+<\/jats:sup>\u2010sensitization mediated by Rho kinase is involved in agonist\u2010 or depolarization\u2010induced contraction of rat epididymal vas deferens. It is the major contractile mechanism underlying noradrenaline\u2010induced Ca<jats:sup>2+<\/jats:sup>\u2010free responses. It contributes to Ca<jats:sup>2+<\/jats:sup>\u2010dependent rhythmic contractility and optimizes the development of full contractile tension triggered through calmodulin\/MLCK activation by stimulated influx of Ca<jats:sup>2+<\/jats:sup>.<\/jats:p>","DOI":"10.1111\/j.1474-8673.2006.00367.x","type":"journal-article","created":{"date-parts":[[2006,3,20]],"date-time":"2006-03-20T13:31:34Z","timestamp":1142861494000},"page":"169-181","source":"Crossref","is-referenced-by-count":15,"title":["Attenuation of contractility in rat epididymal vas deferens by Rho kinase inhibitors"],"prefix":"10.1111","volume":"26","author":[{"given":"N. I. 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