BACKGROUND: Recently, it has been suggested that in vascular smooth muscle a Ca(2+)-independent mechanism or Ca(2+)-sensitization of contractile elements may participate in smooth muscle contraction. In this study, we evaluate this mechanism in detrusor muscle. METHODS: Strips of smooth muscle from rabbit aorta, rabbit bladder and human bladder were evaluated by in vitro contraction studies. RESULTS: The results show that (1) in Ca(2+)-free solution containing ethyleneglycol bis (-aminothylether)-N,N,-tetraacetic acid (EGTA), carbachol and phorbol ester produced sustained contractions in detrusor muscle (Ca(2+)-free contraction); (2) depletion of Ca2+ stores by caffeine did not affect Ca(2+)-free contraction induced by carbachol; and (3) W-7 (calmodulin inhibitor) and ML-9 (myosin light chain kinase [MLCK] inhibitor) did not show inhibitory effects on Ca(2+)-free contraction, while H-7 (protein kinase C. [PKC] inhibitor) abolished this contraction. CONCLUSIONS: These results suggest that neither stored Ca2+ nor the Ca(2+)-calmodulin-MLCK system is involved in the carbachol-induced Ca(2+)-free contraction of detrusor muscle. This Ca(2+)-independent contraction seems to be mediated by the activation of PKC coupled with agonist stimulation of the muscarinic receptor.
BACKGROUND: Recently, it has been suggested that in vascular smooth muscle a Ca(2+)-independent mechanism or Ca(2+)-sensitization of contractile elements may participate in smooth muscle contraction. In this study, we evaluate this mechanism in detrusor muscle. METHODS: Strips of smooth muscle from rabbit aorta, rabbit bladder and human bladder were evaluated by in vitro contraction studies. RESULTS: The results show that (1) in Ca(2+)-free solution containing ethyleneglycol bis (-aminothylether)-N,N,-tetraacetic acid (EGTA), carbachol and phorbol ester produced sustained contractions in detrusor muscle (Ca(2+)-free contraction); (2) depletion of Ca2+ stores by caffeine did not affect Ca(2+)-free contraction induced by carbachol; and (3) W-7 (calmodulin inhibitor) and ML-9 (myosin light chain kinase [MLCK] inhibitor) did not show inhibitory effects on Ca(2+)-free contraction, while H-7 (protein kinase C. [PKC] inhibitor) abolished this contraction. CONCLUSIONS: These results suggest that neither stored Ca2+ nor the Ca(2+)-calmodulin-MLCK system is involved in the carbachol-induced Ca(2+)-free contraction of detrusor muscle. This Ca(2+)-independent contraction seems to be mediated by the activation of PKC coupled with agonist stimulation of the muscarinic receptor.