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Rucaparib-mediated vasodilation of rat vascular tissue may be partially dependent on myosin light chain kinase.

By Cian M. McCrudden (276127), Martin G. O’Rourke (692861), Kim E. Cherry (692862), Hiu-Fung Yuen (276126), Declan O’Rourke (692863), Muhammad Babur (692864), Brian A. Telfer (692865), Huw D. Thomas (114714), Patrick Keane (692866), Thiagarajan Nambirajan (692867), Chris Hagan (692868), Joe M. O’Sullivan (275899), Chris Shaw (285026), Kaye J. Williams (692869), Nicola J. Curtin (351064), David G. Hirst (282406) and Tracy Robson (282407)

Abstract

<p>Panel A; rucaparib (closed squares), nicotinamide (open squares) and ML-9 (open triangles) inhibit smooth muscle contraction in PE-constricted rat tail artery. Artery sections were constricted using 10 μM PE before perfusion with a solution containing 10 μM PE plus the relevant concentration of drug. Panel B; rucaparib, nicotinamide and ML-9 inhibit smooth muscle contraction in PE-constricted rat aorta. Panel C; inhibition of arterial smooth muscle contraction by rucaparib is dependent on a mechanism in addition to MLCK inhibition. Constricted vessel segments were relaxed to the maximal degree achievable with ML-9, before being challenged with a relaxing cocktail of ML-9 plus rucaparib. The histograms illustrate the additive effects that were observed in the cases of both tail artery (left) and aorta (right). ** p<0.01, *** p<0.001 versus relaxation evoked by rucaparib alone; <sup>ΔΔ</sup> p<0.01 versus ML-9 alone. Bars represent mean of at least three independent experiments. Arteries from at least three rats were used per test. Error bars represent SEM. Panel D; rucaparib (closed squares) inhibits MLCK activity with ten times the potency of ML-9 (open triangles). Kinase activity was analyzed using the Millipore IC<sub>50</sub><i>Profiler</i> Express service. Points represent results of duplicate experiments. Error bars represent SEM.</p

Topics: Biological Sciences, MLCK inhibition, nad, dilation, Involves Myosin Light Chain Kinase, PARP inhibitor, rucaparib, dorsal window chamber, P 2 purinergic receptors, potentiating response, Therapeutic inhibition, vasodilation, time tumor vessel perfusion analyses, nitric oxide synthesis, additive relaxation, receptor subtypes, nicotinamide pharmacophore, P 2 Receptors, tantalising evidence, Complex Process, muscle contraction mediator myosin light chain kinase, Indiscriminate blockade, ag, Cancer treatment, Muscle contraction
Year: 2015
DOI identifier: 10.1371/journal.pone.0118187.g001
OAI identifier: oai:figshare.com:article/1311155
Provided by: FigShare
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