Calcium dependency of aortic smooth muscle cell migration induced by 12-l-hydroxy-5,8,10,14-eicosatetraenoic acid. Effects of A23187, Nicardipine and Trifluoperazine

Junko Nakao, Hideki Ito, Toshiro Ooyama, Wen Chang Chang, Sei itsu Murota

Research output: Contribution to journalArticle

89 Citations (Scopus)

Abstract

We have previously reported that 12-l-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE), a 12-lipoxygenase product of arachidonic acid in platelets, is a potent chemoattractant for rat aortic smooth muscle cells. In the present study, the mechanism involved in 12-HETE-associated smooth muscle cell migration was investigated in relation to calcium mobilization in the cells. Migration of smooth muscle cells was measured by a filter membrane technique in modified Boyden chambers. Smooth muscle cell migration induced by 12-HETE increased with the increase of extracellular Ca2+ concentration and became maximal at the physiological Ca2+ concentration of 1.25 mM. The calcium ionophore A23187, at concentrations of 0.2 and 2.0 μM, significantly stimulated cell migration. Nicardipine, a potent calcium-entry blocker, significantly inhibited 12-HETE-associated smooth muscle cell migration at concentrations from 10-9 to 10-5 M. Concentrations of trifluoperazine from 10-9 to 10-5 M and W-7 at 10-5 M, which are specific inhibitors of calmodulin, also significantly inhibited cell migration induced by 12-HETE. Cytochalasin B at 1.0 and 10 μM, and colchicine at 0.1 and 1.0 μM concentrations drastically inhibited cell migration, indicating that actin-containing microfilaments and microtubules are involved in smooth muscle cell migration. These findings indicated that the stimulation of smooth muscle cell migration by 12-HETE is a highly calcium-dependent process and suggest that 12-HETE might act at the initial stage of smooth muscle cell migration through enhancing calcium influx through plasma membrane and thus stimulating cell migration.

Original languageEnglish
Pages (from-to)309-319
Number of pages11
JournalAtherosclerosis
Volume46
Issue number3
DOIs
Publication statusPublished - 1983
Externally publishedYes

Fingerprint

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
Nicardipine
Trifluoperazine
Calcimycin
Smooth Muscle Myocytes
Cell Movement
Calcium
Arachidonate 12-Lipoxygenase
Cytochalasin B
Calcium Ionophores
Chemotactic Factors
Colchicine
Calmodulin
Actin Cytoskeleton
Microtubules
Blood Platelets

Keywords

  • 12-l-hydroxy-5,8,10,14-eicosatetraenoic acid
  • A23187
  • Calcium
  • Nicardipine
  • Smooth muscle cell migration
  • Trifluoperazine

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Calcium dependency of aortic smooth muscle cell migration induced by 12-l-hydroxy-5,8,10,14-eicosatetraenoic acid. Effects of A23187, Nicardipine and Trifluoperazine. / Nakao, Junko; Ito, Hideki; Ooyama, Toshiro; Chang, Wen Chang; Murota, Sei itsu.

In: Atherosclerosis, Vol. 46, No. 3, 1983, p. 309-319.

Research output: Contribution to journalArticle

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abstract = "We have previously reported that 12-l-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE), a 12-lipoxygenase product of arachidonic acid in platelets, is a potent chemoattractant for rat aortic smooth muscle cells. In the present study, the mechanism involved in 12-HETE-associated smooth muscle cell migration was investigated in relation to calcium mobilization in the cells. Migration of smooth muscle cells was measured by a filter membrane technique in modified Boyden chambers. Smooth muscle cell migration induced by 12-HETE increased with the increase of extracellular Ca2+ concentration and became maximal at the physiological Ca2+ concentration of 1.25 mM. The calcium ionophore A23187, at concentrations of 0.2 and 2.0 μM, significantly stimulated cell migration. Nicardipine, a potent calcium-entry blocker, significantly inhibited 12-HETE-associated smooth muscle cell migration at concentrations from 10-9 to 10-5 M. Concentrations of trifluoperazine from 10-9 to 10-5 M and W-7 at 10-5 M, which are specific inhibitors of calmodulin, also significantly inhibited cell migration induced by 12-HETE. Cytochalasin B at 1.0 and 10 μM, and colchicine at 0.1 and 1.0 μM concentrations drastically inhibited cell migration, indicating that actin-containing microfilaments and microtubules are involved in smooth muscle cell migration. These findings indicated that the stimulation of smooth muscle cell migration by 12-HETE is a highly calcium-dependent process and suggest that 12-HETE might act at the initial stage of smooth muscle cell migration through enhancing calcium influx through plasma membrane and thus stimulating cell migration.",
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