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  • Title: Contractile signaling pathways in mouse prostate smooth muscle.
    Author: Kitazawa T.
    Journal: Prostate; 2013 Jun; 73(9):996-1006. PubMed ID: 23389830.
    Abstract:
    BACKGROUND: Prostate smooth muscle plays an important role in the physiological ejection of prostatic fluid and also in the pathogenesis of benign prostate hyperplasia. Although mouse is the best genetically engineered animal model to identify potential molecular targets for human diseases, only fragmentary information is available for basic mechanism of mouse prostate contraction. METHODS: Small smooth muscle tubular rings were excised from four mouse prostate lobes to measure their isometric contractions. High K(+) , noradrenaline (NA), or acetylcholine (ACh) was applied with and without various antagonists and/or inhibitors to examine the contractile signaling pathways. RESULTS: Maximum amplitude of agonist-induced contractions varied greatly with different lobes but not with different locations or orientations within each lobe. Both NA and ACh produced large contractions in ventral and dorsal rings, whereas only small contractions were elicited in lateral and anterior rings. Combination of alpha-1 and muscarinic antagonists suppressed K(+) depolarization-induced contraction potently in ventral rings, but slightly in anterior rings. Blocking of either Ca(2+) -release or Ca(2+) -influx reduced agonist-induced contraction of ventral rings, however, a considerable amount of contractility remained even with both blockers. Inhibitors of ROCK and PKC partially inhibited NA-induced contractions, whereas a combination of Ca(2+) -blockers and Ca(2+) -sensitization inhibitors strongly suppressed the contraction. CONCLUSIONS: The ejection of prostatic fluid is differentially regulated in each prostate lobe. In ventral prostate smooth muscle, Ca(2+) -release, Ca(2+) -influx, and ROCK- and PKC-mediated Ca(2+) -sensitizations are all involved in NA-induced contractions. This finding is a useful step toward the understanding of the phenotypic changes in the smooth muscle of BPH prostate.
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