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10.1371/journal.pone.0154460

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suck abstract from ncbi


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pmid27136356
      PLoS+One 2016 ; 11 (5 ): e0154460
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  • Papaverine Prevents Vasospasm by Regulation of Myosin Light Chain Phosphorylation and Actin Polymerization in Human Saphenous Vein #MMPMID27136356
  • Hocking KM ; Putumbaka G ; Wise ES ; Cheung-Flynn J ; Brophy CM ; Komalavilas P
  • PLoS One 2016[]; 11 (5 ): e0154460 PMID27136356 show ga
  • OBJECTIVE: Papaverine is used to prevent vasospasm in human saphenous veins (HSV) during vein graft preparation prior to implantation as a bypass conduit. Papaverine is a nonspecific inhibitor of phosphodiesterases, leading to increases in both intracellular cGMP and cAMP. We hypothesized that papaverine reduces force by decreasing intracellular calcium concentrations ([Ca2+]i) and myosin light chain phosphorylation, and increasing actin depolymerization via regulation of actin regulatory protein phosphorylation. APPROACH AND RESULTS: HSV was equilibrated in a muscle bath, pre-treated with 1 mM papaverine followed by 5 ?M norepinephrine, and force along with [Ca2+]i levels were concurrently measured. Filamentous actin (F-actin) level was measured by an in vitro actin assay. Tissue was snap frozen to measure myosin light chain and actin regulatory protein phosphorylation. Pre-treatment with papaverine completely inhibited norepinephrine-induced force generation, blocked increases in [Ca2+]i and led to a decrease in the phosphorylation of myosin light chain. Papaverine pre-treatment also led to increased phosphorylation of the heat shock-related protein 20 (HSPB6) and the vasodilator stimulated phosphoprotein (VASP), as well as decreased filamentous actin (F-actin) levels suggesting depolymerization of actin. CONCLUSIONS: These results suggest that papaverine-induced force inhibition of HSV involves [Ca2+]i-mediated inhibition of myosin light chain phosphorylation and actin regulatory protein phosphorylation-mediated actin depolymerization. Thus, papaverine induces sustained inhibition of contraction of HSV by the modulation of both myosin cross-bridge formation and actin cytoskeletal dynamics and is a pharmacological alternative to high pressure distention to prevent vasospasm.
  • |Actins/*metabolism [MESH]
  • |Calcium/metabolism [MESH]
  • |Humans [MESH]
  • |Immunoblotting [MESH]
  • |Muscle, Smooth, Vascular/drug effects/metabolism [MESH]
  • |Myosin Light Chains/*metabolism [MESH]
  • |Papaverine/*pharmacology [MESH]
  • |Phosphorylation/drug effects [MESH]
  • |Saphenous Vein/*drug effects/*metabolism [MESH]


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