Differential effects of a K + channel agonist and Ca 2+ antagonists on myosin light chain phosphorylation in relaxation of endothelin-1-contracted tracheal smooth muscle

Katoch, Surender S.; Rüegg, J. C.; Pfitzer, Gabriele

doi:10.1007/s004240050302

Cited by 10 publications

(6 citation statements)

References 32 publications

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“…Our data support the notion that dephosphorylation of myosin light chain seems not be the essential event in the molecular mechanism of vasodilators elevating cyclic nucleotides, and are in line with the view, that their major mechanism is to lower cytosolic Ca 2ϩ . Apparently, dephosphorylation of myosin light chain does not always occur when cytosolic Ca 2ϩ is reduced [Katoch et al, 1997] In summary, our results demonstrate the phosphorylation of phospholamban in the intact pig coronary artery in response to the potent vasodilators NO, adenosine, and prostacyclin. A strong correlation was obtained between the phosphorylation state of phospholamban and changes in the vessel diameter.…”

Section: Discussionmentioning

confidence: 76%

“…The physiological significance of this effect, however, has not been demonstrated under in vivo conditions. Dephosphorylation of the regulatory myosin light chain is thought to be an important mechanism but does not always correlate with, or is not sufficient to fully explain, smooth muscle relaxation [Gerthoffer et al, 1984;Miller et al, 1983;Katoch et al, 1997]. Relaxation of vascular smooth muscle critically depends on the removal of Ca 2ϩ ions from the cytosol.…”

mentioning

confidence: 97%

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Phosphorylation of phospholamban correlates with relaxation of coronary artery induced by nitric oxide, adenosine, and prostacyclin in the pig

Karczewski¹,

Hendrischke²,

Wolf³

et al. 1998

J. Cell. Biochem.

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The intracellular mechanisms underlying the action of the endogenous vasodilators such as NO/EDRF, adenosine, and prostacyclin acting through cGMP and cAMP, respectively, are not well understood. One important action of cyclic nucleotides in smooth muscle relaxation is to lower the cytosolic Ca2+ concentration by enhanced sequestration into the sarcoplasmic reticulum. The present study was undertaken to elucidate the potential role of phosphorylation of phospholamban, the regulator of sarcoplasmic reticulum Ca2+ pump, for the control of coronary vascular tone by NO/EDRF, adenosine, and prostacyclin. Phospholamban was identified in pig coronary artery preparations by immunofluorescence microscopy, Western blotting and in vitro phosphorylation. Segments of pig coronary artery, with either intact or denuded endothelium, were precontracted with prostaglandin F2alpha (PGF2alpha). In endothelium-denuded preparations 3-morpholinosydnonimine (SIN-1), 5'-N-ethylcarboxiamidoadenosine (NECA), and iloprost (ILO) caused both relaxation and phospholamban phosphorylation with the potency: SIN-1 > NECA > ILO. The regulatory myosin light chain was significantly dephosphorylated only by SIN-1. In endothelium-intact pig coronary artery, L-NAME caused additional vasoconstriction and a decrease in phospholamban phosphorylation, while phosphorylation of myosin light chain remained unchanged. An inverse relationship between phospholamban phosphorylation and vessel tone was obtained. Our findings demonstrate significant phospholamban phosphorylation during coronary artery relaxation evoked by NO, prostacyclin, and adenosine receptor activation. Because of the close correlation between phosphorylation of phospholamban and vessel relaxation, we propose that phospholamban phosphorylation is an important mechanism by which endogenous vasodilators, especially endothelial NO/EDRF, control coronary vascular smooth muscle tone.

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Section: Discussionmentioning

confidence: 76%

mentioning

confidence: 97%

Phosphorylation of phospholamban correlates with relaxation of coronary artery induced by nitric oxide, adenosine, and prostacyclin in the pig

Karczewski¹,

Hendrischke²,

Wolf³

et al. 1998

J. Cell. Biochem.

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“…1990 ), some Ca 2+ depletion protocols ( Gerthoffer 1986, Rembold 1991) or Ca 2+ channel blockers ( D'Angelo, et al. 1992 , Katoch, et al. 1997 ), and other combinations of excitatory and inhibitory stimuli ( Bárány & Bárány 1993, 1996).…”

Section: Physiological Significance Of No and Other Inhibitory Signalsmentioning

confidence: 99%

Inhibitory mechanisms for cross‐bridge cycling: the nitric oxide‐cGMP signal transduction pathway in smooth muscle relaxation

Murphy

Walker

1998

Acta Physiologica Scandinavica

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Relaxation follows sequestration of Ca2+ mobilized by an excitatory stimulus in striated muscle. Removal of excitatory stimuli also relaxes smooth muscle in vitro after reductions in the myoplasmic [Ca2+] and dephosphorylation of the myosin regulatory light chains. However, there are several experimental procedures that produce relaxation in the presence of excitatory stimuli and elevated Ca(2+)-dependent cross-bridge phosphorylation. Of potential widespread physiological importance are treatments that increase myoplasmic [cGMP] owing to the ubiquity of nitric oxide (NO) as a signalling molecule for endothelial-mediated vasodilation and inhibitory nerves in most types of smooth muscle. Several mechanisms are implicated in the NO-cGMP mediated relaxation. Most studies support reductions in myoplasmic Ca2+. However, there is evidence that increases in cGMP also lower the Ca(2+)-sensitivity of cross-bridge phosphorylation. This would contribute to a decline in force through actions on the myosin light chain kinase/phosphatase system. In addition, changes in the dependence of force on phosphorylation are observed in tissues partially relaxed by treatments that elevate cGMP. This demonstrates that either the attachment and cycling of phosphorylated cross-bridges is impaired or blocked, or that the formation of dephosphorylated, force-generating cross-bridges ('latch-bridges') is reduced. Protein kinase G-catalysed phosphorylation of either a thin filament protein that blocks attachment of cross-bridges or a protein that inhibits myosin light chain phosphatase may explain the NO-induced relaxation with elevated cross-bridge phosphorylation.

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“…One mechanism is deactivation, in which reductions in myoplasmic Ca 2ϩ concentration ([Ca 2ϩ ] i ) or increases in myosin phosphatase activity induce relaxation by reducing myosin regulatory light chain (MRLC) phosphorylation. Other treatments that induce force suppression include okadaic acid (22), some Ca 2ϩ -depletion protocols (8), Ca 2ϩ channel blockers (12), high extracellular Mg 2ϩ concentration ([Mg 2ϩ ] o ) (6), and other combinations of excitatory and inhibitory stimuli (2). Force suppression can be observed with increased cGMP concentration induced by nitric oxide (NO) (13), phosphodiesterase inhibitors (5), or increased cAMP concentration (20).…”

mentioning

confidence: 99%

Heat shock protein 20-mediated force suppression in forskolin-relaxed swine carotid artery

Meeks¹,

Ripley²,

Jin³

et al. 2005

American Journal of Physiology-Cell Physiology

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Increases in cyclic nucleotide levels induce smooth muscle relaxation by deactivation [reductions in myosin regulatory light chain (MRLC) phosphorylation (e.g., by reduced [Ca(2+)])] or force suppression (reduction in force without reduction in MRLC phosphorylation). Ser(16)-heat shock protein 20 (HSP20) phosphorylation is the proposed mediator of force suppression. We evaluated three potential hypotheses whereby Ser(16)-HSP20 phosphorylation could regulate smooth muscle force: 1) a threshold level of HSP20 phosphorylation could inactivate a thin filament as a whole, 2) phosphorylation of a single HSP20 could fully inactivate a small region of a thin filament, or 3) HSP20 phosphorylation could weakly inhibit myosin binding at either the thin- or thick-filament level. We tested these hypotheses by analyzing the dependence of force on Ser(16)-HSP20 phosphorylation in swine carotid media. First, we determined that swine HSP20 has a second phosphorylation site at Ser(157). Ser(157)-HSP20 phosphorylation values were high and did not change during contractile activation or forskolin-induced relaxation. Forskolin significantly increased Ser(16)-HSP20 phosphorylation. The relationship between Ser(16)-HSP20 phosphorylation and force remained linear and was shifted downward in partially activated muscles relaxed with forskolin. Neither forskolin nor nitroglycerin induced actin depolymerization as detected using the F/G-actin ratio method in smooth muscle homogenates. These results suggest that force suppression does not occur in accordance with the first hypothesis (inactivation of a thin filament as a whole). Our data are more consistent with the second and third hypotheses that force suppression is mediated by full or partial inhibition of local myosin binding at the thin- or thick-filament level.

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Differential effects of a K + channel agonist and Ca 2+ antagonists on myosin light chain phosphorylation in relaxation of endothelin-1-contracted tracheal smooth muscle

Cited by 10 publications

References 32 publications

Phosphorylation of phospholamban correlates with relaxation of coronary artery induced by nitric oxide, adenosine, and prostacyclin in the pig

Phosphorylation of phospholamban correlates with relaxation of coronary artery induced by nitric oxide, adenosine, and prostacyclin in the pig

Inhibitory mechanisms for cross‐bridge cycling: the nitric oxide‐cGMP signal transduction pathway in smooth muscle relaxation

Heat shock protein 20-mediated force suppression in forskolin-relaxed swine carotid artery

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