| Title | Signalling pathways involved in the contractile response to 5-HT in human pulmonary artery. | | Author(s) | Rodat-Despoix L, Aires V, Ducret T, Marthan R, Savineau JP, Rousseau E, Guibert C | | Institution | U885, Laboratoire de Physiologie Cellulaire Respiratoire, F-33076 Bordeaux, France; and Université Bordeaux 2, F-33076 Bordeaux, France. | | Source | Eur Respir J 2009 Jun 18. | | Abstract | 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. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19541711 |
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