PMID- 18671941
OWN - NLM
STAT- MEDLINE
DCOM- 20080910
LR  - 20211203
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 374
IP  - 4
DP  - 2008 Oct 3
TI  - Insulin-like growth factor-I inhibits rat arterial K(ATP) channels through pI 
      3-kinase.
PG  - 742-6
LID - 10.1016/j.bbrc.2008.07.100 [doi]
AB  - Since, in addition to its growth-promoting actions, insulin-like growth factor-I 
      (IGF-I) has rapid vasoactive actions, we investigated the effects of IGF-I on 
      whole-cell ATP-sensitive K(+) (K(ATP)) currents of rat mesenteric arterial smooth 
      muscle cells. IGF-I (10 or 30 nM) reduced K(ATP) currents activated by pinacidil 
      or a membrane permeant cAMP analogue. Inhibition of phospholipase C, protein 
      kinase C, protein kinase A, mitogen-activated protein kinase or mammalian target 
      of rapamycin (mTOR) did not prevent the action of IGF-I. However, inhibition of 
      K(ATP) currents by IGF-I was abolished by the tyrosine kinase inhibitor genistein 
      or the phosphoinositide 3-kinase inhibitors, LY 294002 and wortmannin. 
      Intracellular application of either phosphatidylinositol 4,5-bisphosphate 
      (PIP(2)) or phosphatidylinositol 3,4,5-trisphosphate (PIP(3)) increased the 
      K(ATP) current activated by pinacidil and abolished the inhibitory effect of 
      IGF-I. Thus, we show regulation of arterial K(ATP) channels by 
      polyphosphoinositides and report for the first time that IGF-I inhibits these 
      channels via a phosphoinositide 3-kinase-dependent pathway.
FAU - Hayabuchi, Y
AU  - Hayabuchi Y
AD  - Department of Cell Physiology and Pharmacology, Ion Channel Group, University of 
      Leicester, P.O. Box 138, Leicester LE1 9HN, UK.
FAU - Willars, G B
AU  - Willars GB
FAU - Standen, N B
AU  - Standen NB
FAU - Davies, N W
AU  - Davies NW
LA  - eng
GR  - British Heart Foundation/United Kingdom
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080729
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Androstadienes)
RN  - 0 (Chromones)
RN  - 0 (KATP Channels)
RN  - 0 (Morpholines)
RN  - 0 (Phosphatidylinositol 4,5-Diphosphate)
RN  - 0 (Phosphatidylinositol Phosphates)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (phosphatidylinositol 3,4,5-triphosphate)
RN  - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - 7B0ZZH8P2W (Pinacidil)
RN  - DH2M523P0H (Genistein)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.1.4.11 (Phosphoinositide Phospholipase C)
RN  - XVA4O219QW (Wortmannin)
SB  - IM
MH  - Androstadienes/pharmacology
MH  - Animals
MH  - Arteries/drug effects/enzymology/*metabolism
MH  - Chromones/pharmacology
MH  - Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors/metabolism
MH  - Genistein/pharmacology
MH  - Insulin-Like Growth Factor I/pharmacology/*physiology
MH  - KATP Channels/*antagonists & inhibitors/metabolism
MH  - Male
MH  - Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism
MH  - Morpholines/pharmacology
MH  - Myocytes, Smooth Muscle/drug effects/enzymology/*metabolism
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Phosphatidylinositol 4,5-Diphosphate/pharmacology
MH  - Phosphatidylinositol Phosphates/pharmacology
MH  - Phosphoinositide Phospholipase C/antagonists & inhibitors/metabolism
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Pinacidil/pharmacology
MH  - Protein Kinase C/antagonists & inhibitors/metabolism
MH  - Protein Kinases/metabolism
MH  - Protein-Tyrosine Kinases/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - TOR Serine-Threonine Kinases
MH  - Wortmannin
EDAT- 2008/08/02 09:00
MHDA- 2008/09/11 09:00
CRDT- 2008/08/02 09:00
PHST- 2008/07/17 00:00 [received]
PHST- 2008/07/18 00:00 [accepted]
PHST- 2008/08/02 09:00 [pubmed]
PHST- 2008/09/11 09:00 [medline]
PHST- 2008/08/02 09:00 [entrez]
AID - S0006-291X(08)01448-4 [pii]
AID - 10.1016/j.bbrc.2008.07.100 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2008 Oct 3;374(4):742-6. doi: 
      10.1016/j.bbrc.2008.07.100. Epub 2008 Jul 29.