HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 297/2/H726    most recent 00312.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Wang, W. Articles by Muthuchamy, M. PubMed PubMed Citation Articles by Wang, W. Articles by Muthuchamy, M.

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

¹Department of Systems Biology and Translational Medicine, Cardiovascular Research Institute Division of Lymphatic Biology, Texas A&M Health Science Center College of Medicine, College Station/Temple, Texas; and ²Department of Medical Pharmacology and Physiology, University of Missouri School of Medicine, Columbia, Missouri

Submitted 30 March 2009 ; accepted in final form 11 June 2009

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 (MLC₂₀) plays an essential role in blood vessel smooth muscle contraction, we investigated if phosphorylated MLC₂₀ (pMLC₂₀) 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 cmH₂O) and substance P (SP; 10^–7 M). Immunohistochemical and Western blot analyses of pMLC₂₀ were also performed on isolated lymphatics. The results showed that 1) increasing pressure decreased both the lymphatic tonic contraction strength and pMLC₂₀-to-MLC₂₀ ratio; 2) SP increased both the tonic contraction strength and phosphorylation of MLC₂₀; 3) ML-7 decreased both the lymphatic tonic contraction strength and pMLC₂₀-to-MLC₂₀ 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 MLC₂₀ 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.

ML-7; lymphatic contraction; tonic contraction; phasic contraction