Activation of the JAK/STAT pathway in vascular smooth muscle by serotonin

Amy K.L. Banes, Seán M. Shaw, Amany Tawfik, Bela P. Patel, Safia Ogbi, David Fulton, Mario B. Marrero

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

Serotonin (5-hydroxytryptamine, 5-HT) is a vasoconstrictor and mitogen whose levels are elevated in diabetes. Previous studies have shown the presence of 5-HT2A, 5-HT2B, and 5-HT1B receptors in vascular smooth muscle cells (VSMCs). There are currently no data regarding 5-HT2B and 5-HT1B receptor activation of the JAK/STAT pathway in VSMCs and resultant potential alterations in 5-HT signaling in diabetes. Therefore, we tested the hypothesis that 5-HT differentially activates the JAK/ STAT pathway in VSMCs under conditions of normal (5 mM) and high (25 mM) glucose. Treatment of rat VSMCs with 5-HT (10-6 M) resulted in time-dependent activation (∼2-fold) of JAK2, JAK1, and STAT1, but not STAT3 (maximal at 5 min, returned to baseline by 30 min). The 5-HT2B receptor agonist BW723C86 and the 5-HT1B receptor agonist CGS12066A (10-9-10-5 M, 5-min stimulation) did not activate the JAK/STAT pathway. Treatment with the 5-HT2A receptor antagonist ketanserin (10 nM) inhibited JAK2 activation by 5-HT. Treatment of streptozotocin-induced diabetic rats with ketanserin (5 mg·kg -1·day-1) reduced activation of JAK2 and STAT1 but not STAT3 in endothelium-denuded thoracic aorta in vivo. 5-HT (10-6 M) treatment resulted in increased cell proliferation and increased DNA synthesis, which were inhibited by the JAK2 inhibitor AG490. Further studies with apocynin, diphenyleneiodonium chloride, catalase, and virally transfected superoxide dismutase had no effect at either glucose concentration on activation of the JAK/STAT pathway by 5-HT. Therefore, we conclude that 5-HT activates JAK2, JAK1, and STAT1 via the 5-HT2A receptors in a reactive oxygen species-independent manner under both normal and high glucose conditions.

Original languageEnglish (US)
Pages (from-to)C805-C812
JournalAmerican Journal of Physiology - Cell Physiology
Volume288
Issue number4 57-4
DOIs
StatePublished - Apr 2005

Keywords

  • 5-hydroxytryptamine
  • Reactive oxygen species

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

Fingerprint Dive into the research topics of 'Activation of the JAK/STAT pathway in vascular smooth muscle by serotonin'. Together they form a unique fingerprint.

  • Cite this