PI3-kinase/Akt modulates vascular smooth muscle tone via cAMP signaling pathways

Padmini Komalavilas, Shyamal Mehta, Christopher J. Wingard, Daniel T. Dransfield, Jyoti Bhalla, Julie E. Woodrum, Jason R. Molinaro, Colleen M. Brophy

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Phosphatidylinositol 3-kinase (PI3-kinase) activates protein kinase B (also known as Akt), which phosphorylates and activates a cyclic nucleotide phosphodiesterase 3B. Increases in cyclic nucleotide concentrations inhibit agonist-induced contraction of vascular smooth muscle. Thus we hypothesized that the PI3-kinase/Akt pathway may regulate vascular smooth muscle tone. In unstimulated, intact bovine carotid artery smooth muscle, the basal phosphorylation of Akt was higher than that in cultured smooth muscle cells. The phosphorylation of Akt decreases in a time-dependent manner when incubated with the PI3-kinase inhibitor, LY-294002. Agonist (serotonin)-, phorbol ester (phorbol 12,13-dibutyrate; PDBu)-, and depolarization (KCl)-induced contractions of vascular smooth muscles were all inhibited in a dose-dependent fashion by LY-294002. However, LY-294002 did not inhibit serotonin- or PDBu-induced increases in myosin light chain phosphorylation or total O2 consumption, suggesting that inhibition of contraction was not mediated by reversal or inhibition of the pathways that lead to smooth muscle activation and contraction. Treatment of vascular smooth muscle with LY-294002 increased the activity of cAMP-dependent protein kinase and increased the phosphorylation of the cAMP-dependent protein kinase substrate heat shock protein 20 (HSP20). These data suggest that activation of the PI3-kinase/Akt pathway in unstimulated smooth muscle may modulate vascular smooth muscle tone (allow agonist-induced contraction) through inhibition of the cyclic nucleotide/HSP20 pathway and suggest that cyclic nucleotide-dependent inhibition of contraction is dissociated from the myosin light chain contractile regulatory pathways.

Original languageEnglish (US)
Pages (from-to)1819-1827
Number of pages9
JournalJournal of applied physiology
Volume91
Issue number4
DOIs
StatePublished - Jan 1 2001

Keywords

  • Myosin light chains
  • Phorbol ester
  • Serotonin
  • cAMP-dependent protein kinase

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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    Komalavilas, P., Mehta, S., Wingard, C. J., Dransfield, D. T., Bhalla, J., Woodrum, J. E., Molinaro, J. R., & Brophy, C. M. (2001). PI3-kinase/Akt modulates vascular smooth muscle tone via cAMP signaling pathways. Journal of applied physiology, 91(4), 1819-1827. https://doi.org/10.1152/jappl.2001.91.4.1819