PMID- 11568168
OWN - NLM
STAT- MEDLINE
DCOM- 20011204
LR  - 20211203
IS  - 8750-7587 (Print)
IS  - 0161-7567 (Linking)
VI  - 91
IP  - 4
DP  - 2001 Oct
TI  - PI3-kinase/Akt modulates vascular smooth muscle tone via cAMP signaling pathways.
PG  - 1819-27
AB  - 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 O(2) 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.
FAU - Komalavilas, P
AU  - Komalavilas P
AD  - Institute for Molecular Medicine and Genetics, Medical College of Georgia, 
      Augusta, GA 30912, USA.
FAU - Mehta, S
AU  - Mehta S
FAU - Wingard, C J
AU  - Wingard CJ
FAU - Dransfield, D T
AU  - Dransfield DT
FAU - Bhalla, J
AU  - Bhalla J
FAU - Woodrum, J E
AU  - Woodrum JE
FAU - Molinaro, J R
AU  - Molinaro JR
FAU - Brophy, C M
AU  - Brophy CM
LA  - eng
GR  - R01 HL-58027-01/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Appl Physiol (1985)
JT  - Journal of applied physiology (Bethesda, Md. : 1985)
JID - 8502536
RN  - 0 (Chromones)
RN  - 0 (Enzyme Activators)
RN  - 0 (Heat-Shock Proteins)
RN  - 0 (Morpholines)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one)
RN  - 37558-16-0 (Phorbol 12,13-Dibutyrate)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - EC 2.7.11.18 (Myosin-Light-Chain Kinase)
SB  - IM
MH  - Animals
MH  - Carotid Arteries/physiology
MH  - Cattle
MH  - Chromones/pharmacology
MH  - Cyclic AMP/*physiology
MH  - Cyclic AMP-Dependent Protein Kinases/metabolism
MH  - Enzyme Activators/pharmacology
MH  - Female
MH  - Heat-Shock Proteins/metabolism
MH  - Isoelectric Focusing
MH  - Morpholines/pharmacology
MH  - Muscle Contraction/drug effects/physiology
MH  - Muscle, Smooth, Vascular/enzymology/*physiology
MH  - Myosin-Light-Chain Kinase/metabolism
MH  - Oxygen Consumption/physiology
MH  - Phorbol 12,13-Dibutyrate/pharmacology
MH  - Phosphatidylinositol 3-Kinases/*physiology
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Phosphorylation
MH  - Pregnancy
MH  - *Protein Serine-Threonine Kinases
MH  - Proto-Oncogene Proteins/*physiology
MH  - Proto-Oncogene Proteins c-akt
MH  - Signal Transduction/*physiology
EDAT- 2001/09/25 10:00
MHDA- 2002/01/05 10:01
CRDT- 2001/09/25 10:00
PHST- 2001/09/25 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/09/25 10:00 [entrez]
AID - 10.1152/jappl.2001.91.4.1819 [doi]
PST - ppublish
SO  - J Appl Physiol (1985). 2001 Oct;91(4):1819-27. doi: 10.1152/jappl.2001.91.4.1819.