Nitric oxide inhibits serotonin-induced calcium release in pulmonary artery smooth muscle cells

Xiao Jian Yuan, Rose T. Bright, Ann M. Aldinger, Lewis J. Rubin

Research output: Contribution to journalArticlepeer-review

43 Scopus citations


Nitric oxide (NO) is a potent endothelium-derived pulmonary vasodilator. Serotonin (5-HT; 10-50 μM) constricts pulmonary artery (PA) by releasing Ca2+ from intracellular stores and promoting Ca2+ influx through Ca2+ channels in PA smooth muscle cells (PASMC). The effect of NO on 5-HT-induced increase in cytosolic free Ca2+ concentration ([Ca2+]) in rat PASMC was investigated to elucidate whether inhibition of agonist-mediated Ca2+ rise is involved in the NO-mediated pulmonary vasodilation. The 5-HT-induced increase in [Ca2+](i) was characterized by a transient (because of Ca2+ release from intracellular stores) followed by a plateau (because of Ca2+ influx). Removal of extracellular Ca2+ eliminated the 5-HT-induced [Ca2+](i) plateau, but insignificantly affected the [Ca2+](i) transient. In some of the PASMC bathed in the Ca2+-containing or Ca2+-free solution, 5-HT also induced Ca2+ oscillations. Pretreatment of the cells with 10 μM cyclopiazonic acid (CPA) abolished, whereas 10 mM caffeine negligibly affected, the 5-HT-induced [Ca2+](i) transients in the absence of external Ca2+. Authentic NO (~0.3 μM) reversibly diminished 5-HT-induced [Ca2+](i) transients but augmented CPA-induced Ca2+ release in the absence of extracellular Ca2+. NO also significantly inhibited 5-HT- induced [Ca2+](i) plateau in PASMC bathed in Ca2+-containing solution, suggesting that NO inhibits both agonist-induced Ca2+ release from the CPA- sensitive Ca2+ stores and Ca2+ influx from extracellular fluid. These data suggest that NO-induced inhibition of the evoked increases in [Ca2+](i) and augmentation of Ca2+ sequestration into intracellular stores in PASMC are involved in the mechanisms by which NO causes pulmonary vasodilation.

Original languageEnglish (US)
Pages (from-to)L44-L50
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number1 16-1
StatePublished - Jan 1997
Externally publishedYes


  • caffeine
  • calcium oscillation
  • cyclopiazonic acid
  • inositol 1,4,5-trisphosphate-sensitive calcium store

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology


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