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Accueil > Bibliographie > Signalling pathways involved in the contractile response to 5-HT in human (...)

Signalling pathways involved in the contractile (...)

Eur Respir J. 2009 Jun ; [Epub ahead of print]
Signalling pathways involved in the contractile response to 5-HT in human pulmonary artery.
Rodat-Despoix L, Aires V, Ducret T, Marthan R, Savineau JP, Rousseau E, Guibert C.

Serotonin (5-HT) is a potent pulmonary vasoconstrictor and mitogenic agent whose plasma level is increased in pulmonary hypertensive patients. Thus, we explored the signalling pathways involved in the contractile response to 5-HT in human pulmonary arteries (HPA).Intact and beta-escin permeabilized rings from HPA mounted in an organ bath system were used to assess both tension and myofilament Ca(2+)-sensitization. Microspectrofluorimetry was used for intracellular Ca(2+) recordings in cultured HPA smooth muscle cells.Voltage-operated Ca(2+) channel blockers (nitrendipine and nifedipine) partially reduced the contraction to 5-HT. Thapsigargin or cyclopiazonic acid (CPA), known to deplete sarcoplasmic reticulum-Ca(2+) stores, also partially inhibited the contraction whereas removal of extracellular Ca(2+) in those conditions further inhibited the contraction. Changing from Ca(2+)-free to Ca(2+) containing solution, in the presence of nitrendipine and CPA, a protocol known to stimulate store-operated Ca(2+) channels, induced HPA contractions which were blocked by nickel. Nickel or gadolinium also reduced the contraction to 5-HT. Finally, 5-HT increased intracellular Ca(2+) responses in cultured HPA smooth muscle cells and myofilament Ca(2+)-sensitization in HPA rings.Collectively, these results indicate that voltage-operated and voltage-independent Ca(2+) channels, as well as Ca(2+) release and myofilament Ca(2+)-sensitization participate to 5-HT-induced contraction in HPA.

PubMed

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