PMID- 22364165
OWN - NLM
STAT- MEDLINE
DCOM- 20121009
LR  - 20211021
IS  - 1476-5381 (Electronic)
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 166
IP  - 4
DP  - 2012 Jun
TI  - The relationship between the MMP system, adrenoceptors and phosphoprotein 
      phosphatases.
PG  - 1225-43
LID - 10.1111/j.1476-5381.2012.01917.x [doi]
AB  - The MMPs and their inhibitors [tissue inhibitor of MMPs (TIMPs)] form the 
      mainstay of extracellular matrix homeostasis. They are expressed in response to 
      numerous stimuli including cytokines and GPCR activation. This review highlights 
      the importance of adrenoceptors and phosphoprotein phosphatases (PPP) in 
      regulating MMPs in the cardiovascular system, which may help explain some of the 
      beneficial effects of targeting the adrenoceptor system in tissue remodelling and 
      will establish emerging crosstalk between these three systems. Although alpha- and 
      beta-adrenoceptor activation increases MMP but decreases TIMP expression, MMPs are 
      implicated in the growth stimulatory effects of adrenoceptor activation through 
      transactivation of epidermal growth factor receptor. Furthermore, they have 
      recently been found to catalyse the proteolysis of beta-adrenoceptors and modulate 
      vascular tone. While the mechanisms underpinning these effects are not well 
      defined, reversible protein phosphorylation by kinases and phosphatases may be 
      key. In particular, PPP (Ser/Thr phosphatases) are not only critical in 
      resensitization and internalization of adrenoceptors but also modulate MMP 
      expression. The interrelationship is complex as isoprenaline (ISO) inhibits 
      okadaic acid [phosphoprotein phosphatase type 1/phosphoprotein phosphatase type 
      2A (PP2A) inhibitor]-mediated MMP expression. While this may be simply due to its 
      ability to transiently increase PP2A activity, there is evidence for MMP-9 that 
      ISO prevents okadaic acid-mediated expression of MMP-9 through a beta-arrestin, 
      NF-kappaB-dependent pathway, which is abolished by knock-down of PP2A. It is 
      essential that crosstalk between MMPs, adrenoceptors and PPP are investigated 
      further as it will provide important insight into how adrenoceptors modulate 
      cardiovascular remodelling, and may identify new targets for pharmacological 
      manipulation of the MMP system.
CI  - (c) 2012 The Authors. British Journal of Pharmacology (c) 2012 The British 
      Pharmacological Society.
FAU - Rietz, A
AU  - Rietz A
AD  - Department of Pharmacology and Therapeutics, Trinity College Dublin, Dublin, 
      Ireland.
FAU - Spiers, Jp
AU  - Spiers J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Adrenergic Agonists)
RN  - 0 (Adrenergic Antagonists)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Matrix Metalloproteinase Inhibitors)
RN  - 0 (Receptors, Adrenergic)
RN  - EC 3.1.3.16 (Phosphoprotein Phosphatases)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
SB  - IM
MH  - Adrenergic Agonists/pharmacology/therapeutic use
MH  - Adrenergic Antagonists/pharmacology/therapeutic use
MH  - Animals
MH  - Enzyme Activation/drug effects
MH  - Enzyme Inhibitors/pharmacology/therapeutic use
MH  - Gene Expression Regulation, Enzymologic/drug effects
MH  - Humans
MH  - Matrix Metalloproteinase Inhibitors
MH  - Matrix Metalloproteinases/chemistry/genetics/*metabolism
MH  - Molecular Targeted Therapy
MH  - Phosphoprotein Phosphatases/antagonists & inhibitors/chemistry/*metabolism
MH  - Phosphorylation/drug effects
MH  - Protein Processing, Post-Translational/drug effects
MH  - Protein Transport/drug effects
MH  - Proteolysis/drug effects
MH  - Receptors, Adrenergic/*metabolism
MH  - Signal Transduction/drug effects
PMC - PMC3417442
EDAT- 2012/03/01 06:00
MHDA- 2012/10/10 06:00
PMCR- 2013/06/01
CRDT- 2012/02/28 06:00
PHST- 2012/02/28 06:00 [entrez]
PHST- 2012/03/01 06:00 [pubmed]
PHST- 2012/10/10 06:00 [medline]
PHST- 2013/06/01 00:00 [pmc-release]
AID - 10.1111/j.1476-5381.2012.01917.x [doi]
PST - ppublish
SO  - Br J Pharmacol. 2012 Jun;166(4):1225-43. doi: 10.1111/j.1476-5381.2012.01917.x.