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

Citation
P. Komalavilas et al., PI3-kinase/Akt modulates vascular smooth muscle tone via cAMP signaling pathways, J APP PHYSL, 91(4), 2001, pp. 1819-1827
Citations number
39
Categorie Soggetti
Physiology
Journal title
JOURNAL OF APPLIED PHYSIOLOGY
ISSN journal
87507587 → ACNP
Volume
91
Issue
4
Year of publication
2001
Pages
1819 - 1827
Database
ISI
SICI code
8750-7587(200110)91:4<1819:PMVSMT>2.0.ZU;2-1
Abstract
Phosphatidylinositol 3-kinase (PI3-kinase) activates protein kinase B (also known as Akt), which phosphorylates and activates a cyclic nucleotide phos phodiesterase 3B. Increases in cyclic nucleotide concentrations inhibit ago nist-induced contraction of vascular smooth muscle. Thus we hypothesized th at the PI3-kinase/Akt pathway may regulate vascular smooth muscle tone. In unstimulated, intact bovine carotid artery smooth muscle, the basal phospho rylation of Akt was higher than that in cultured smooth muscle cells. The p hosphorylation of Akt decreases in a time-dependent manner when incubated w ith the PI3-kinase inhibitor, LY-294002. Agonist (serotonin)-, phorbol este r (phorbol 12,13-dibutyrate; PDBu)-, and depolarization (KCI)-induced contr actions of vascular smooth muscles were all inhibited in a dose-dependent f ashion by LY-294002. However, LY-294002 did not inhibit serotonin- or PDBu- induced increases in myosin light chain phosphorylation or total O-2 consum ption, suggesting that inhibition of contraction was not mediated by revers al or inhibition of the pathways that lead to smooth muscle activation and contraction. Treatment of vascular smooth muscle with LY-294002 increased t he activity of cAMP-dependent protein kinase and increased the phosphorylat ion of the cAMP-dependent protein kinase substrate heat shock protein 20 (H SP20). 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/HS P20 pathway and suggest that cyclic nucleotide-dependent inhibition of cont raction is dissociated from the myosin light chain contractile regulatory p athways.