Focal Adhesion Kinase Activation is Involved in Contractile Stimulation-induced Detrusor Muscle Contraction in Mice
Document Type
Article
Publication Date
8-6-2023
Publication Title
European Journal of Pharmacology
Abstract
Recent studies suggested smooth muscle contraction may involve mechanisms besides the myosin regulatory light chain (MLC) phosphorylation-induced actomyosin crossbridge cycling. This study aims to determine if focal adhesion kinase (FAK) activation is involved in mouse detrusor muscle contraction. The mouse detrusor muscle strips were preincubated with PF-573228 (2 & mu;M), latrunculin B (1 & mu;M), or the same volume of vehicle (DMSO) for 30 min. The contractile responses to KCl (90 mM), electrical field stimulation (EFS, 2-32 Hz), or carbachol (CCh, 10-7.5-10-4.5 M) were measured. In a separate experiment, the phosphorylated FAK (p-FAK) and MLC (p-MLC) levels were measured in the detrusor strips stimulated with CCh (10 & mu;M) after incubation with PF-573228 or vehicle (DMSO) compared to those with vehicle incubation but without CCh stimulation. KCl-induced contractile responses decreased significantly after incubation with PF-573228 or latrunculin B compared to the corresponding vehicle-treated strips (p < 0.0001). The contractile responses induced by EFS were markedly inhibited by preincubation with PF-573228 at 8, 16, and 32 Hz (p < 0.05) or latrunculin B at 16 and 32 Hz (p < 0.01). Following the application of PF-573228 or Latrunculin B, CCh-induced dose-response contractions were lower than the corresponding vehicle group (p = 0.0021 and 0.0003, respectively). Western blot examination showed that CCh stimulation enhanced the expression of p-FAK and p-MLC, while preincubation with PF-573228 pre-vented the increase of p-FAK but not p-MLC. In conclusion, FAK activation involves tension development induced by contractile stimulation in the mouse detrusor muscle. This effect is likely caused by promoting actin polymerization rather than elevating MLC phosphorylation.
Recommended Citation
Maher, Shaimaa; Bayachou, Mekki; Fu, Pingfu; Hijaz, Adonis; and Liu, Guiming, "Focal Adhesion Kinase Activation is Involved in Contractile Stimulation-induced Detrusor Muscle Contraction in Mice" (2023). Chemistry Faculty Publications. 635.
https://engagedscholarship.csuohio.edu/scichem_facpub/635
DOI
10.1016/j.ejphar.2023.175807
Volume
952
Comments
GL was supported by the National Institutes of Health (NIH)/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grant R01-DK110567.