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Cited by 64Lymphatic System and DiseasesLymphatic Disorders and TreatmentsGastrointestinal motility and disorders

Inhibition of myosin light chain phosphorylation decreases rat mesenteric lymphatic contractile activity

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Wang, Wei, Nepiyushchikh, Zhanna, Zawieja, David C., Chakraborty, Sanjukta, Zawieja, Scott D., Gashev, Anatoliy A., Davis, Michael J., Muthuchamy, Mariappan·2009·American Journal of Physiology-Heart and Circulatory Physiology
DOI 10.1152/ajpheart.00312.2009PMC PMC2724206
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Abstract

Muscular lymphatics use both phasic and tonic contractions to transport lymph for conducting their vital functions. The molecular mechanisms regulating lymphatic muscle contractions are not well understood. Based on the well-established finding that the phosphorylation of myosin light chain 20 (MLC 20) plays an essential role in blood vessel smooth muscle contraction, we investigated if phosphorylated MLC 20(pMLC 20) would modulate the tonic and/or phasic contractions of lymphatic muscle. The effects of ML-7, a MLC kinase inhibitor (1–10 μM), were tested on the contractile parameters of isolated and cannulated rat mesenteric lymphatics during their responses to the known modulators, pressure (1–5 cmH 2 O) and substance P (SP; 10−7 M). Immunohistochemical and Western blot analyses of pMLC 20 were also performed on isolated lymphatics. The results showed that 1) increasing pressure decreased both the lymphatic tonic contraction strength and pMLC 20-to-MLC 20 ratio; 2) SP increased both the tonic contraction strength and phosphorylation of MLC 20; 3) ML-7 decreased both the lymphatic tonic contraction strength and pMLC 20-to-MLC 20 ratio; and 4) the increase in lymphatic phasic contraction frequency in response to increasing pressure was diminished by ML-7; however, the phasic contraction amplitude was not significantly altered by ML-7 either in the absence or presence of SP. These data provide the first evidence that tonic contraction strength and phasic contraction amplitude of the lymphatics can be differentially regulated, whereby the increase in MLC 20 phosphorylation produces an activation in the tonic contraction without significant changes in the phasic contraction amplitude. Thus, tonic contraction of rat mesenteric lymphatics appears to be MLC kinase dependent.

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  • Spontaneous lymphatic contractions are regulated by the phosphorylation of myosin light chain 20 through the balance of myosin light chain kinase/phosphatase activities.

    “Spontaneous lymphatic contractions are regulated by the phosphorylation of myosin light chain 20 through the balance of myosin light chain kinase/phosphatase activities (62, 63).”

    From Transport and Immune Functions of the Lymphatic System. (2025) · cites this paper as [63]

    The Abstract and Discussion report that MLC20 phosphorylation and MLCK activity regulate tonic contractions in isolated rat mesenteric lymphatics; MLCK inhibition also reduced phasic contraction frequency. But the Discussion says phasic contraction amplitude did not appear to be regulated by MLC20 phosphorylation under the tested conditions, and the paper does not establish a kinase–phosphatase balance as the mechanism for spontaneous lymphatic contractions generally. (LLM, conf=0.88)

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Cited by

Sorted by citations

Authors
Wang, W., Nepiyushchikh, Z., Zawieja, D. C., Chakraborty, S., Zawieja, S. D., Gashev, A. A., Davis, M. J., & Muthuchamy, M.
Affiliations
Texas A&M Health Science Center (US)
ORCID
Venue
American Journal of Physiology-Heart and Circulatory Physiology
Publisher
American Physiological Society
Published
2009-08
Volume
297
Issue
2
Pages
H726-H734
ISSN
  • 0363-6135 (ISSN-L)
  • 1522-1539
DOI
10.1152/ajpheart.00312.2009
PMC
PMC2724206
OpenAlex
W2124073510
Cited by
64
References
1
Citations by year
2024: 2 · 2023: 5 · 2022: 7 · 2021: 4 · 2020: 1 · 2019: 5 · 2018: 2 · 2017: 5 · 2016: 3 · 2015: 7 · 2014: 6 · 2013: 3 · 2012: 3
FWCI
2.33
Type
journal article
Language
en
Open access
Locations
  • American Journal of Physiology-Heart and Circulatory Physiology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Lymphatic Research Foundation
  • National Heart, Lung, and Blood Institute (HL-80526, R01HL070308, KO2HL-86650, R01HL080526, K02HL086650, HL75199, R01HL075199)
Topics
  • Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
  • Health Sciences › Medicine › Surgery › Lymphatic Disorders and Treatments
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
Keywords
myosin light chain 20 phosphorylation, ML-7, substance P, tonic contraction, phasic contractions, lymphatic transport, mesenteric lymphatics, lymphatic pressure
MeSH terms
Animals, Azepines, Enzyme Inhibitors, Immunohistochemistry, Lymphatic System, Male, Mesentery, Muscle Contraction, Muscle, Smooth, Naphthalenes, Phosphorylation, Pressure, Rats, Sprague-Dawley, Myosin Light Chains, Rats

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