The role of PKC and Rho-kinase in the control of force–calcium relationship evoked by carbachol-induced SR calcium release in smooth muscle

Resveratrol (3,5,4′-trihydroxystilbene) is a chemical compound belonging to the group of polyphenols and flavonoids. The aim of the present study was to determine the influence of resveratrol application along with certain modulating factors, such as 8Br-cGMP-activator of cGMP-dependent protein kinases, HA-1077-Rho-kinase inhibitor, and Bay K8644-calcium channel agonist, on VMSCs constriction triggered by phenylephrine. Resveratrol at a dose of 10 mg/kg/24 h administered for 4 weeks reduced the reactivity of the arteries to the pressure action of catecholamines. Tests performed after four weeks of resveratrol administration showed that 8Br-cGMP at the concentrations of 0.01 mM/l and 0.1 mM/l intensifies this effect. Simultaneous resveratrol and Bay K8644 administration led to a significant decrease in contractility compared to the vessels collected from animals (Res−). This effect was dependent on the concentration of Bay K8644. Resveratrol seems to be counteractive against Bay K8644 by blocking L-type calcium channels. As the concentration of HA-1077 increased, there was a marked hyporeactivity of the vessels to the pressure effects of phenylephrine. The results indicate synergy between resveratrol and Rho-kinase inhibition.

Download Full-text

Activation of Rho signaling contributes to lysophosphatidic acid-induced contraction of intact ileal smooth muscle of guinea-pig

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y00-050 ◽

2000 ◽

Vol 78 (9) ◽

pp. 729-736 ◽

Cited By ~ 15

Author(s):

Mayumi Mori ◽

Hiromi Tsushima

Keyword(s):

Smooth Muscle ◽

Guinea Pig ◽

Lysophosphatidic Acid ◽

Membrane Fraction ◽

Smooth Muscles ◽

Rho Kinase ◽

Specific Inhibitor ◽

High K ◽

Rho A

To elucidate the possible role of Rho A/Rho-kinase on lysophosphatidic acid (LPA)-induced contraction in intact guinea-pig ileal smooth muscle, we examined effects of pretreatment with a specific inhibitor of Rho-kinase (Y-27632) on the LPA-induced contraction and MLC20 phosphorylation. In addition, we investigated whether LPA actually elicits an activation of Rho A by studying subcellular distribution of Rho A in unstimulated and stimulated smooth muscles by LPA. LPA induced a less intense, but sustained, contraction compared with ACh, and was accompanied by significant increases in MLC20 phosphorylation. The effects of LPA on tension and MLC20 phosphorylation were inhibited by Y-27632. The ACh-induced contraction, but not increases in MLC20 phosphorylation, was partially inhibited by Y-27632. High K+-induced contraction was unaffected by the inhibitor. LPA stimulated translocation of Rho A from the cytosol to the membrane fraction of the muscle. Translocation of Rho A was also induced by ACh and high K+. These results suggest that LPA-induced contraction of intact ileal smooth muscle is dominated through activation of Rho A and Rho-kinase and subsequent increases in MLC20 phosphorylation.Key words: lysophosphatidic acid, Rho, Rho-kinase, ileal smooth muscle.

Download Full-text

Role of rho-kinase (ROCK) in tonic but not phasic contraction in the frog stomach smooth muscle

Life Sciences ◽

10.1016/j.lfs.2018.02.023 ◽

2018 ◽

Vol 198 ◽

pp. 46-55 ◽

Cited By ~ 1

Author(s):

Leyla Sahin ◽

Ozge Selin Cevik ◽

Dilan Deniz Koyuncu ◽

Kansu Buyukafsar

Keyword(s):

Smooth Muscle ◽

Rho Kinase ◽

Phasic Contraction ◽

Frog Stomach

Download Full-text

373 Role of myosin light chain kinase and Rho kinase in carbachol-induced contractions of human detrusor smooth muscle

European Urology Supplements ◽

10.1016/s1569-9056(12)60370-4 ◽

2012 ◽

Vol 11 (1) ◽

pp. e373

Author(s):

C. Protzel ◽

T. Kirschstein ◽

K. Porath ◽

T. Sellmann ◽

R. Koehling ◽

...

Keyword(s):

Smooth Muscle ◽

Light Chain ◽

Myosin Light Chain Kinase ◽

Myosin Light Chain ◽

Rho Kinase ◽

Detrusor Smooth Muscle ◽

Human Detrusor

Download Full-text

Effect of changes in pH on wall tension in isolated rat pulmonary artery: role of the RhoA/Rho-kinase pathway

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00331.2003 ◽

2004 ◽

Vol 287 (4) ◽

pp. L673-L684 ◽

Cited By ~ 21

Author(s):

Jean-Marc Hyvelin ◽

Clare O’Connor ◽

Paul McLoughlin

Keyword(s):

Smooth Muscle ◽

Vascular Smooth Muscle ◽

Kinase Inhibitor ◽

Pulmonary Arteries ◽

Rho Kinase ◽

Systemic Circulation ◽

Pulmonary Vasculature ◽

Tension Development ◽

Kinase Pathway

Pulmonary arteries (PA) are resistant to the vasodilator effects of extracellular acidosis in systemic vessels; the mechanism underlying this difference between systemic and pulmonary circulations has not been elucidated. We hypothesized that RhoA/Rho-kinase-mediated Ca2+ sensitization pathway played a greater role in tension development in pulmonary than in systemic vascular smooth muscle and that this pathway was insensitive to acidosis. In arterial rings contracted with the α1-agonist phenylephrine (PE), the Rho-kinase inhibitor Y-27632 (≤3 μM) induced greater relaxation in precontracted PA rings than in aortic rings. In PA rings stimulated by PE, the activation of RhoA was greater than in aorta. Normocapnic acidosis (NA) induced a smaller relaxation in precontracted PA than in aorta. However, in the presence of nifedipine and thapsigargin, when PE-induced contraction was predominantly mediated by Rho-kinase, the relaxant effect of NA was reduced and similar in both vessel types. Furthermore, in the presence of Y-27632, NA induced a greater relaxation in both PA and aorta, which was similar in both vessels. Finally, in α-toxin-permeabilized smooth muscle, PE-induced contraction at constant Ca2+ activity was inhibited by Y-27632 and unaffected by acidosis. These results indicate that Ca2+ sensitization induced by the RhoA/Rho-kinase pathway played a greater role in agonist-induced vascular smooth muscle contraction in PA than in aorta and that tension mediated by this pathway was insensitive to acidosis. The predominant role of the RhoA/Rho-kinase pathway in the pulmonary vasculature may account for the resistance of this circulation to the vasodilator effect of acidosis observed in the systemic circulation.

Download Full-text

RYR2 Proteins Contribute to the Formation of Ca2+ Sparks in Smooth Muscle

The Journal of General Physiology ◽

10.1085/jgp.200308999 ◽

2004 ◽

Vol 123 (4) ◽

pp. 377-386 ◽

Cited By ~ 53

Author(s):

Guangju Ji ◽

Morris E. Feldman ◽

Kai Su Greene ◽

Vincenzo Sorrentino ◽

Hong-Bo Xin ◽

...

Keyword(s):

Smooth Muscle ◽

Calcium Release ◽

Ryanodine Receptors ◽

Wild Type ◽

Calcium Dependent ◽

Outward Currents ◽

Associated Proteins ◽

Kinetics Of ◽

Spontaneous Transient Outward Currents

Calcium release through ryanodine receptors (RYR) activates calcium-dependent membrane conductances and plays an important role in excitation-contraction coupling in smooth muscle. The specific RYR isoforms associated with this release in smooth muscle, and the role of RYR-associated proteins such as FK506 binding proteins (FKBPs), has not been clearly established, however. FKBP12.6 proteins interact with RYR2 Ca2+ release channels and the absence of these proteins predictably alters the amplitude and kinetics of RYR2 unitary Ca2+ release events (Ca2+ sparks). To evaluate the role of specific RYR2 and FBKP12.6 proteins in Ca2+ release processes in smooth muscle, we compared spontaneous transient outward currents (STOCs), Ca2+ sparks, Ca2+-induced Ca2+ release, and Ca2+ waves in smooth muscle cells freshly isolated from wild-type, FKBP12.6−/−, and RYR3−/− mouse bladders. Consistent with a role of FKBP12.6 and RYR2 proteins in spontaneous Ca2+ sparks, we show that the frequency, amplitude, and kinetics of spontaneous, transient outward currents (STOCs) and spontaneous Ca2+ sparks are altered in FKBP12.6 deficient myocytes relative to wild-type and RYR3 null cells, which were not significantly different from each other. Ca2+ -induced Ca2+ release was similarly augmented in FKBP12.6−/−, but not in RYR3 null cells relative to wild-type. Finally, Ca2+ wave speed evoked by CICR was not different in RYR3 cells relative to control, indicating that these proteins are not necessary for normal Ca2+ wave propagation. The effect of FKBP12.6 deletion on the frequency, amplitude, and kinetics of spontaneous and evoked Ca2+ sparks in smooth muscle, and the finding of normal Ca2+ sparks and CICR in RYR3 null mice, indicate that Ca2+ release through RYR2 molecules contributes to the formation of spontaneous and evoked Ca2+ sparks, and associated STOCs, in smooth muscle.

Download Full-text