Myosin light chain phosphorylation in intact rat uterine smooth muscle. Role of calcium and cyclic AMP

1986 ◽  
Vol 7 (3) ◽  
pp. 259-268 ◽  
Author(s):  
Lien Dokhac ◽  
Anne D'Albis ◽  
Chantal Janmot ◽  
Simone Harbon
Keyword(s):  
Smooth Muscle ◽  
Cyclic Amp ◽  
Light Chain ◽  
Myosin Light Chain ◽  
Myosin Light Chain Phosphorylation ◽  
Uterine Smooth Muscle

Effects of cGMP on [Ca2+]i, myosin light chain phosphorylation, and contraction in human myometrium

1991 ◽  
Vol 260 (4) ◽  
pp. C861-C867 ◽  
Author(s):  
R. A. Word ◽  
M. L. Casey ◽  
K. E. Kamm ◽  
J. T. Stull
Keyword(s):  
Smooth Muscle ◽  
Light Chain ◽  
Myosin Light Chain ◽  
Smooth Muscles ◽  
Smooth Muscle Relaxation ◽  
Human Myometrium ◽  
Myosin Light Chain Phosphorylation ◽  
Cyclic Monophosphate ◽  
Uterine Smooth Muscle ◽  
Spontaneous Contractions

Adenosine 3',5'-cyclic monophosphate (cAMP) is believed to be an important mediator of myometrial relaxation, and there is evidence to suggest that guanosine 3',5'-cyclic monophosphate (cGMP) is a mediator of smooth muscle relaxation in vascular and probably nonvascular tissues. To investigate the biochemical mechanisms involved in regulation of human myometrial contractility, we studied the effects of analogues of cAMP and cGMP, as well as activators of adenylate and guanylate cyclases, on uterine smooth muscle contractile activity. We found that myometrial smooth muscle cells in culture respond to analogues of cGMP and cAMP, as well as activators of guanylate cyclase, with a significant decrease in the resting and endothelin-induced increase in [Ca2+]i. Treatment of human uterine smooth muscle strips with sodium nitroprusside or isoproterenol results in diminished force and frequency of contraction as well as a decrease in the rate and extent of myosin light chain phosphorylation in spontaneous contractions of human myometrium. cGMP did not effect relaxation of endothelin-stimulated contractions of human myometrium, but the relaxation effects of cGMP were dramatic in precontracted bovine tracheal and human fetal aortic smooth muscles. Whereas cGMP and cAMP act to promote a decrease in the force and frequency of spontaneous contractions in human myometrium, this tissue is not as responsive to the actions of cyclic nucleotides as are other types of smooth muscle.

Role of myosin light-chain phosphorylation in guinea pig gallbladder smooth muscle contraction

1994 ◽  
Vol 266 (3) ◽  
pp. G469-G474 ◽  
Author(s):  
R. J. Washabau ◽  
M. B. Wang ◽  
C. Dorst ◽  
J. P. Ryan
Keyword(s):  
Smooth Muscle ◽  
Steady State ◽  
Light Chain ◽  
Myosin Light Chain ◽  
Smooth Muscle Contraction ◽  
Myosin Light Chain Phosphorylation ◽  
Shortening Velocity ◽  
Cross Bridges ◽  
Isotonic Shortening

In acetylcholine (ACh)-stimulated gallbladder smooth muscle, we have previously shown that phosphorylation of the 20,000-Da myosin light chains is necessary for the initiation of contraction, that myosin is stably phosphorylated at steady state, and that dephosphorylation of cross bridges is not necessary for the slowing of cross-bridge cycling rates during the period of steady-state isometric stress. The present studies were undertaken to determine whether 1) K+ (60 or 80 mM) or cholecystokinin (CCK, 10(-8) M) stimulation is accompanied by changes in myosin light-chain phosphorylation in gallbladder smooth muscle and 2) dephosphorylated noncycling cross bridges exist in K(+)- or CCK-stimulated gallbladder smooth muscle. Isometric stress, isotonic shortening velocity, and myosin light-chain phosphorylation were determined during contraction with K+ or CCK. Steady-state isometric stress was reached within 2.5 min of stimulation with K+ or CCK and was maintained for the duration of the stimulation. Stimulation with K+ or CCK was associated with rapid increases in myosin light-chain phosphorylation and maintenance of myosin light-chain phosphorylation during the stimulation. In contrast, isotonic shortening velocity was maximal at 1 min of stimulation with either K+ or CCK and then declined significantly to values that were only 26-32% of the peak velocity. These data, along with data from previous experiments with ACh, suggest that myosin light-chain phosphorylation is essential in the initiation of contraction in gallbladder smooth muscle, regardless of the source of Ca2+ or of the contractile agonist.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Clostridium difficiletoxin B inhibits carbachol-induced force and myosin light chain phosphorylation in guinea-pig smooth muscle: role of Rho proteins

1998 ◽  
Vol 506 (1) ◽  
pp. 83-93 ◽  
Author(s):  
Claudia Lucius ◽  
Anders Arner ◽  
Annette Steusloff ◽  
Monika Troschka ◽  
Fred Hofmann ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Guinea Pig ◽  
Light Chain ◽  
Myosin Light Chain ◽  
Myosin Light Chain Phosphorylation ◽  
Rho Proteins

scholarly journals Arteriolar vasodilation involves actin depolymerization

2018 ◽  
Vol 315 (2) ◽  
pp. H423-H428
Author(s):  
Philip S. Clifford ◽  
Brian S. Ferguson ◽  
Jeffrey L. Jasperse ◽  
Michael A. Hill
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Sodium Nitroprusside ◽  
Light Chain ◽  
Myosin Light Chain ◽  
Muscle Relaxation ◽  
Nitric Oxide Donor ◽  
Smooth Muscle Relaxation ◽  
Myosin Light Chain Phosphorylation ◽  
Actin Depolymerization

It is generally assumed that relaxation of arteriolar vascular smooth muscle occurs through hyperpolarization of the cell membrane, reduction in intracellular Ca2+ concentration, and activation of myosin light chain phosphatase/inactivation of myosin light chain kinase. We hypothesized that vasodilation is related to depolymerization of F-actin. Cremaster muscles were dissected in rats under pentobarbital sodium anesthesia (50 mg/kg). First-order arterioles were dissected, cannulated on glass micropipettes, pressurized, and warmed to 34°C. Internal diameter was monitored with an electronic video caliper. The concentration of G-actin was determined in flash-frozen intact segments of arterioles by ultracentrifugation and Western blot analyses. Arterioles dilated by ~40% of initial diameter in response to pinacidil (1 × 10−6 mM) and sodium nitroprusside (5 × 10−5 mM). The G-actin-to-smooth muscle 22α ratio was 0.67 ± 0.09 in arterioles with myogenic tone and increased significantly to 1.32 ± 0.34 ( P < 0.01) when arterioles were dilated with pinacidil and 1.14 ± 0.18 ( P < 0.01) with sodium nitroprusside, indicating actin depolymerization. Compared with control vessels (49 ± 5%), the percentage of phosphorylated myosin light chain was significantly reduced by pinacidil (24 ± 2%, P < 0.01) but not sodium nitroprusside (42 ± 4%). These findings suggest that actin depolymerization is an important mechanism for vasodilation of resistance arterioles to external agonists. Furthermore, pinacidil produces smooth muscle relaxation via both decreases in myosin light chain phosphorylation and actin depolymerization, whereas sodium nitroprusside produces smooth muscle relaxation primarily via actin depolymerization. NEW & NOTEWORTHY This article adds to the accumulating evidence on the contribution of the actin cytoskeleton to the regulation of vascular smooth muscle tone in resistance arterioles. Actin depolymerization appears to be an important mechanism for vasodilation of resistance arterioles to pharmacological agonists. Dilation to the K+ channel opener pinacidil is produced by decreases in myosin light chain phosphorylation and actin depolymerization, whereas dilation to the nitric oxide donor sodium nitroprusside occurs primarily via actin depolymerization. Listen to this article’s corresponding podcast at https://ajpheart.podbean.com/e/vascular-smooth-muscle-actin-depolymerization/ .

scholarly journals Role of myosin light chain kinase in regulation of basal blood pressure and maintenance of salt-induced hypertension

2011 ◽  
Vol 301 (2) ◽  
pp. H584-H591 ◽  
Author(s):  
Wei-Qi He ◽  
Yan-Ning Qiao ◽  
Cheng-Hai Zhang ◽  
Ya-Jing Peng ◽  
Chen Chen ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Smooth Muscle ◽  
Light Chain ◽  
Myosin Light Chain Kinase ◽  
Myosin Light Chain ◽  
Vascular Tone ◽  
Induced Hypertension ◽  
Basal Blood Pressure ◽  
Muscle Myosin

Vascular tone, an important determinant of systemic vascular resistance and thus blood pressure, is affected by vascular smooth muscle (VSM) contraction. Key signaling pathways for VSM contraction converge on phosphorylation of the regulatory light chain (RLC) of smooth muscle myosin. This phosphorylation is mediated by Ca2+/calmodulin-dependent myosin light chain kinase (MLCK) but Ca2+-independent kinases may also contribute, particularly in sustained contractions. Signaling through MLCK has been indirectly implicated in maintenance of basal blood pressure, whereas signaling through RhoA has been implicated in salt-induced hypertension. In this report, we analyzed mice with smooth muscle-specific knockout of MLCK. Mesenteric artery segments isolated from smooth muscle-specific MLCK knockout mice (MLCKSMKO) had a significantly reduced contractile response to KCl and vasoconstrictors. The kinase knockout also markedly reduced RLC phosphorylation and developed force. We suggest that MLCK and its phosphorylation of RLC are required for tonic VSM contraction. MLCKSMKO mice exhibit significantly lower basal blood pressure and weaker responses to vasopressors. The elevated blood pressure in salt-induced hypertension is reduced below normotensive levels after MLCK attenuation. These results suggest that MLCK is necessary for both physiological and pathological blood pressure. MLCKSMKO mice may be a useful model of vascular failure and hypotension.

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