PMID- 11156937
OWN - NLM
STAT- MEDLINE
DCOM- 20010322
LR  - 20141120
IS  - 0892-6638 (Print)
IS  - 0892-6638 (Linking)
VI  - 15
IP  - 2
DP  - 2001 Feb
TI  - Myosin light-chain kinase regulates endothelial calcium entry and 
      endothelium-dependent vasodilation.
PG  - 282-4
AB  - Activation of smooth muscle myosin light-chain kinase (MLCK) causes contraction. 
      Here we have proven that MLCK controls Ca2+ entry (CE) in endothelial cells 
      (ECs): MLCK antisense oligonucleotides strongly prevented bradykinin (BK)- and 
      thapsigargin (TG)-induced endothelial Ca2+ response, while MLCK sense did not. We 
      also show that the relevant mechanism is not phosphorylation of myosin 
      light-chain (MLC): MLC phosphorylation by BK required CE, but MLC phosphorylation 
      caused by the phosphatase inhibitor calyculin A did not trigger Ca2+ response. 
      Most important, we provide for the first time strong evidence that, in contrast 
      to its role in smooth muscle cells, activation of MLCK in ECs stimulates the 
      production of important endothelium-derived vascular relaxing factors: MLCK 
      antisense and MLCK inhibitors abolished BK- and TG-induced nitric oxide 
      production, and MLCK inhibitors substantially inhibited acetylcholine-stimulated 
      hyperpolarization of smooth muscle cell membrane in rat mesenteric artery. These 
      results indicate that MLCK controls endothelial CE, but not through MLC 
      phosphorylation, and unveils a hitherto unknown physiological function of the 
      enzyme: vasodilation through its action in endothelial cells. The study discovers 
      a counter-balancing role of MLCK in the regulation of vascular tone.
FAU - Watanabe, H
AU  - Watanabe H
AD  - Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School 
      of Medicine, 3600 Handa-cho, Hamamatsu 431-3192, Japan. hwat@hama-med.ac.jp
FAU - Tran, Q K
AU  - Tran QK
FAU - Takeuchi, K
AU  - Takeuchi K
FAU - Fukao, M
AU  - Fukao M
FAU - Liu, M Y
AU  - Liu MY
FAU - Kanno, M
AU  - Kanno M
FAU - Hayashi, T
AU  - Hayashi T
FAU - Iguchi, A
AU  - Iguchi A
FAU - Seto, M
AU  - Seto M
FAU - Ohashi, K
AU  - Ohashi K
LA  - eng
PT  - Journal Article
DEP - 20001208
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Recombinant Proteins)
RN  - 67526-95-8 (Thapsigargin)
RN  - EC 2.7.11.18 (Myosin-Light-Chain Kinase)
RN  - N9YNS0M02X (Acetylcholine)
RN  - S8TIM42R2W (Bradykinin)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Acetylcholine/pharmacology
MH  - Animals
MH  - Bradykinin/*pharmacology
MH  - Calcium/*physiology
MH  - Calcium Signaling/drug effects/*physiology
MH  - Endothelium, Vascular/*physiology
MH  - In Vitro Techniques
MH  - Muscle, Smooth, Vascular/drug effects/*physiology
MH  - Myosin-Light-Chain Kinase/genetics/*metabolism
MH  - Recombinant Proteins/metabolism
MH  - Thapsigargin/pharmacology
MH  - Transfection
MH  - Vasodilation/*physiology
EDAT- 2001/02/07 11:00
MHDA- 2001/03/27 10:01
CRDT- 2001/02/07 11:00
PHST- 2001/02/07 11:00 [pubmed]
PHST- 2001/03/27 10:01 [medline]
PHST- 2001/02/07 11:00 [entrez]
AID - 00-0587fje [pii]
AID - 10.1096/fj.00-0587fje [doi]
PST - ppublish
SO  - FASEB J. 2001 Feb;15(2):282-4. doi: 10.1096/fj.00-0587fje. Epub 2000 Dec 8.