The relaxing effect of dihydrotestosterone on myometrial smooth muscle contraction is mediated via blockage of intracellular calcium increase and inhibition of myosin light chain phosphorylation

2014 ◽  
Author(s):  
Sofia Makieva ◽  
Philippa T K Saunders ◽  
Jane E Norman
Keyword(s):  
Smooth Muscle ◽  
Muscle Contraction ◽  
Intracellular Calcium ◽  
Light Chain ◽  
Myosin Light Chain ◽  
Smooth Muscle Contraction ◽  
Myosin Light Chain Phosphorylation ◽  
Relaxing Effect

Blebbistatin, a myosin II inhibitor, suppresses contraction and disrupts contractile filaments organization of skinned taenia cecum from guinea pig

2010 ◽  
Vol 298 (5) ◽  
pp. C1118-C1126 ◽  
Author(s):  
Masaru Watanabe ◽  
Masatoshi Yumoto ◽  
Hideyuki Tanaka ◽  
Hon Hui Wang ◽  
Takeshi Katayama ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Guinea Pig ◽  
Muscle Contraction ◽  
Light Chain ◽  
Myosin Light Chain ◽  
Myosin Ii ◽  
Smooth Muscle Contraction ◽  
Myosin Light Chain Phosphorylation ◽  
Thin Filaments ◽  
Tension Development

To explore the precise mechanisms of the inhibitory effects of blebbistatin, a potent inhibitor of myosin II, on smooth muscle contraction, we studied the blebbistatin effects on the mechanical properties and the structure of contractile filaments of skinned (cell membrane permeabilized) preparations from guinea pig taenia cecum. Blebbistatin at 10 μM or higher suppressed Ca2+-induced tension development at any given Ca2+ concentration but had little effects on the Ca2+-induced myosin light chain phosphorylation. Blebbistatin also suppressed the 10 and 2.75 mM Mg2+-induced, “myosin light chain phosphorylation-independent” tension development at more than 10 μM. Furthermore, blebbistatin induced conformational change of smooth muscle myosin (SMM) and disrupted arrangement of SMM and thin filaments, resulting in inhibition of actin-SMM interaction irrespective of activation with Ca2+. In addition, blebbistatin partially inhibited Mg2+-ATPase activity of native actomyosin from guinea pig taenia cecum at around 10 μM. These results suggested that blebbistatin suppressed skinned smooth muscle contraction through disruption of structure of SMM by the agent.

scholarly journals A Calponin Peptide Enhances Ca2+Sensitivity of Smooth Muscle Contraction without Affecting Myosin Light Chain Phosphorylation

1995 ◽  
Vol 270 (35) ◽  
pp. 20400-20403 ◽  
Author(s):  
Takeo Itoh ◽  
Akito Suzuki ◽  
Yoshimasa Watanabe ◽  
Terumasa Mino ◽  
Michiko Naka ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Muscle Contraction ◽  
Light Chain ◽  
Myosin Light Chain ◽  
Smooth Muscle Contraction ◽  
Myosin Light Chain Phosphorylation

scholarly journals Rho-associated Kinase Directly Induces Smooth Muscle Contraction through Myosin Light Chain Phosphorylation

1997 ◽  
Vol 272 (19) ◽  
pp. 12257-12260 ◽  
Author(s):  
Yasuko Kureishi ◽  
Sei Kobayashi ◽  
Mutsuki Amano ◽  
Kazushi Kimura ◽  
Hideo Kanaide ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Muscle Contraction ◽  
Light Chain ◽  
Myosin Light Chain ◽  
Smooth Muscle Contraction ◽  
Myosin Light Chain Phosphorylation

Sodium hydrosulfite contractions of smooth muscle are calcium and myosin phosphorylation independent

1998 ◽  
Vol 275 (5) ◽  
pp. L976-L982 ◽  
Author(s):  
Ming-Fu Yu ◽  
Isabelle Gorenne ◽  
Xiaoling Su ◽  
Robert S. Moreland ◽  
Michael I. Kotlikoff
Keyword(s):  
Smooth Muscle ◽  
Muscle Contraction ◽  
Light Chain ◽  
Myosin Light Chain ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Smooth Muscles ◽  
Smooth Muscle Contraction ◽  
Myosin Light Chain Phosphorylation ◽  
Sodium Hydrosulfite ◽  
Pulmonary Arterial

In an effort to further understand the processes underlying hypoxic pulmonary vasoconstriction, we examined the mechanism by which sodium hydrosulfite (Na2S2O4), a potent reducing agent and oxygen scavenger, induces smooth muscle contraction. In rat pulmonary arterial strips, sodium hydrosulfite (10 mM) induced contractions that were 65.9 ± 12.8% of the response to 60 mM KCl ( n = 9 segments). Contractions were not inhibited by nisoldipine (5 μM) or by repeated stimulation with caffeine (10 mM), carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone (10 μM), or cyclopiazonic acid (10 μM), all of which eliminated responses to contractile agonists. Maximum force generation after exposure to sodium hydrosulfite was 0.123 ± 0.013 mN in the presence of 1.8 mM calcium and 0.127 ± 0.015 mN in the absence of calcium. Sodium hydrosulfite contractions in pulmonary arterial segments were not due to the generation of H2O2and occurred in the presence of chelerythrine (10 μM), which blocked phorbol ester contractions, and solution hyperoxygenation. Similar contractile responses were obtained in rat aortic and tracheal smooth muscles. Finally, contractions occurred in the complete absence of an increase in myosin light chain phosphorylation. Therefore sodium hydrosulfite-induced smooth muscle contraction is not specific to pulmonary arterial smooth muscle, is independent of calcium and myosin light chain phosphorylation, and is not mediated by either hypoxia or protein kinase C.

Depletion of focal adhesion kinase by antisense depresses contractile activation of smooth muscle

2001 ◽  
Vol 280 (4) ◽  
pp. C874-C883 ◽  
Author(s):  
Dale D. Tang ◽  
Susan J. Gunst
Keyword(s):  
Smooth Muscle ◽  
Muscle Contraction ◽  
Focal Adhesion Kinase ◽  
Signaling Pathways ◽  
Tyrosine Phosphorylation ◽  
Focal Adhesion ◽  
Light Chain ◽  
Myosin Light Chain ◽  
Smooth Muscle Contraction ◽  
Myosin Light Chain Phosphorylation

Focal adhesion kinase (FAK) undergoes tyrosine phosphorylation in response to the contractile stimulation of tracheal smooth muscle. We hypothesized that FAK may play an important role in signaling pathways that regulate smooth muscle contraction. FAK antisense or FAK sense was introduced into muscle strips by reversible permeabilization, and strips were incubated with antisense or sense for 7 days. Antisense decreased FAK expression compared with that in untreated and sense-treated tissues, but it did not affect the expression of vinculin or myosin light chain kinase. Increases in force, intracellular free Ca2+, and myosin light chain phosphorylation in response to stimulation with ACh or KCl were depressed in FAK-depleted tissues, but FAK depletion did not affect the activation of permeabilized tracheal muscle strips with Ca2+. The tyrosine phosphorylation of paxillin, a substrate for FAK, was also significantly reduced in FAK-depleted strips. We conclude that FAK is a necessary component of the signaling pathways that regulate smooth muscle contraction and that FAK plays a role in regulating intracellular free Ca2+ and myosin light chain phosphorylation.

Calcium-dependent mechanisms of regulation of smooth muscle contraction

1991 ◽  
Vol 69 (12) ◽  
pp. 771-800 ◽  
Author(s):  
Michael P. Walsh
Keyword(s):  
Smooth Muscle ◽  
Muscle Contraction ◽  
Light Chain ◽  
Myosin Light Chain Kinase ◽  
Myosin Light Chain ◽  
Binding Protein ◽  
Smooth Muscle Contraction ◽  
Light Chains ◽  
Contractile State ◽  
Calmodulin Binding

The contractile state of smooth muscle is regulated primarily by the sarcoplasmic (cytosolic) free Ca2+ concentration. A variety of stimuli that induce smooth muscle contraction (e.g., membrane depolarization, α-adrenergic and muscarinic agonists) trigger an increase in sarcoplasmic free [Ca2+] from resting levels of 120–270 to 500–700 nM. At the elevated [Ca2+], Ca2+ binds to calmodulin, the ubiquitous and multifunctional Ca2+-binding protein. The interaction of Ca2+ with CaM induces a conformational change in the Ca2+-binding protein with exposure of a site(s) of interaction with target proteins, the most important of which in the context of smooth muscle contraction is the enzyme myosin light chain kinase. The interaction of calmodulin with myosin light chain kinase results in activation of the kinase that catalyzes phosphorylation of myosin at serine-19 of each of the two 20-kDa light chains (native myosin is a hexamer composed of two heavy chains (230 kDa each) and two pairs of light chains (one pair of 20 kDa each and the other pair of 17 kDa each)). This simple phosphorylation reaction triggers cycling of myosin cross-bridges along actin filaments and the development of force. Relaxation of the muscle follows removal of Ca2+ from the sarcoplasm, whereupon calmodulin dissociates from myosin light chain kinase regenerating the inactive kinase; myosin is dephosphorylated by myosin light chain phosphatase(s), whereupon it dissociates and remains detached from the actin filament and the muscle relaxes. A substantial body of evidence has been accumulated in support of this central role of myosin phosphorylation–dephosphorylation in the regulation of smooth muscle contraction. However, a wide range of physiological and biochemical studies supports the existence of additional, secondary Ca2+-dependent mechanisms that can modulate or fine-tune the contractile state of the smooth muscle cell. Three such mechanisms have emerged: (i) the actin-, tropomyosin-, and calmodulin-binding protein, calponin; (ii) the actin-, myosin-, tropomyosin-, and calmodulin-binding protein, caldesmon; and (iii) the Ca2+- and phospholipid-dependent protein kinase (protein kinase C).Key words: smooth muscle, Ca2+, myosin phosphorylation, regulation of contraction.

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