American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · 2003 · 31 citations · 41 references
MedicinePhysiologyUrologyCell SignalingMechanobiologySignal TransductionDetrusor ActivityDetrusor Muscle FunctionDetrusor OveractivityLower Urinary Tract PhysiologyMuscle PhysiologyOveractive BladderBladder Filling Phase PhysiologyKinase InhibitorsMuscle Fiber LengthMuscle Force-length RelationshipMyosin RegulationPharmacology Of Detrusor ActivityProtein Kinase InhibitorsSmooth Muscle Contraction
Urinary bladder (detrusor) smooth muscle is active in the absence of an external stimulus. Tone occurs even "at rest" during the filling phase, and it is elevated in patients with overactive bladder. This study examined the role of muscle length on tone and the level of basal myosin light chain phosphorylation (MLC(20P)). MLC(20P) was 23.9 +/- 1% (n = 58) at short lengths (zero preload; L(z)). An increase in length from L(z) to the optimal length for contraction (L(o)) caused a reduction in MLC(20P) to 15.8 +/- 1% (n = 49). Whereas 10 microM staurosporine reduced MLC(20P) at L(z), 1 microM staurosporine, a Ca(2+)-free solution, and inhibitors of MLC kinase, protein kinase C (PKC) and RhoA kinase (ROK) did not. However, 1 microM staurosporine and inhibitors of ROK inhibited MLC(20P) and tone at L(o). These data support the hypothesis that a Ca(2+)-independent kinase, possibly ZIP-like kinase, regulates MLC(20P) at L(z), whereas in detrusor stretched to L(o), additional kinases, such as ROK, participate.
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Specificity and mechanism of action of some commonly used protein kinase inhibitors
Stephen Davies, Helen Reddy, Matilde Caivano et al. · Biochemical Journal · 2000 · 4.1K citations · Full text
Specificity and mechanism of action of some commonly used protein kinase inhibitors
Stephen Davies, Helen Reddy, Matilde Caivano et al. · Biochemical Journal · 2000 · 3.1K citations