Abstract
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 language | English (US) |
|---|---|
| Journal | American Journal of Physiology - Lung Cellular and Molecular Physiology |
| Volume | 272 |
| Issue number | 1 16-1 |
| State | Published - Jan 1997 |
| Externally published | Yes |
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Keywords
- caffeine
- calcium oscillation
- cyclopiazonic acid
- inositol 1,4,5-trisphosphate-sensitive calcium store
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
- Cell Biology
- Physiology
- Physiology (medical)
Cite this
Nitric oxide inhibits serotonin-induced calcium release in pulmonary artery smooth muscle cells. / Yuan, Jason; Bright, Rose T.; Aldinger, Ann M.; Rubin, Lewis J.
In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 272, No. 1 16-1, 01.1997.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Nitric oxide inhibits serotonin-induced calcium release in pulmonary artery smooth muscle cells
AU - Yuan, Jason
AU - Bright, Rose T.
AU - Aldinger, Ann M.
AU - Rubin, Lewis J.
PY - 1997/1
Y1 - 1997/1
N2 - 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.
AB - 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.
KW - caffeine
KW - calcium oscillation
KW - cyclopiazonic acid
KW - inositol 1,4,5-trisphosphate-sensitive calcium store
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UR - http://www.scopus.com/inward/citedby.url?scp=0031035835&partnerID=8YFLogxK
M3 - Article
C2 - 9038901
AN - SCOPUS:0031035835
VL - 272
JO - American Journal of Physiology
JF - American Journal of Physiology
SN - 0363-6143
IS - 1 16-1
ER -