PMID- 25032954
OWN - NLM
STAT- MEDLINE
DCOM- 20151208
LR  - 20211203
IS  - 1528-3658 (Electronic)
IS  - 1076-1551 (Print)
IS  - 1076-1551 (Linking)
VI  - 20
IP  - 1
DP  - 2014 Oct 13
TI  - Chemokine (C-X-C motif) receptor 4 and atypical chemokine receptor 3 regulate 
      vascular alpha(1)-adrenergic receptor function.
PG  - 435-47
LID - 10.2119/molmed.2014.00101 [doi]
AB  - Chemokine (C-X-C motif) receptor (CXCR) 4 and atypical chemokine receptor (ACKR) 
      3 ligands have been reported to modulate cardiovascular function in various 
      disease models. The underlying mechanisms, however, remain unknown. Thus, it was 
      the aim of the present study to determine how pharmacological modulation of CXCR4 
      and ACKR3 regulate cardiovascular function. In vivo administration of TC14012, a 
      CXCR4 antagonist and ACKR3 agonist, caused cardiovascular collapse in normal 
      animals. During the cardiovascular stress response to hemorrhagic shock, 
      ubiquitin, a CXCR4 agonist, stabilized blood pressure, whereas coactivation of 
      CXCR4 and ACKR3 with CXC chemokine ligand 12 (CXCL12), or blockade of CXCR4 with 
      AMD3100 showed opposite effects. While CXCR4 and ACKR3 ligands did not affect 
      myocardial function, they selectively altered vascular reactivity upon 
      alpha1-adrenergic receptor (AR) activation in pressure myography experiments. CXCR4 
      activation with ubiquitin enhanced alpha1-AR-mediated vasoconstriction, whereas ACKR3 
      activation with various natural and synthetic ligands antagonized alpha1-AR-mediated 
      vasoconstriction. The opposing effects of CXCR4 and ACKR3 activation by CXCL12 
      could be dissected pharmacologically. CXCR4 and ACKR3 ligands did not affect 
      vasoconstriction upon activation of voltage-operated Ca(2+) channels or 
      endothelin receptors. Effects of CXCR4 and ACKR3 agonists on vascular alpha1-AR 
      responsiveness were independent of the endothelium. These findings suggest that 
      CXCR4 and ACKR3 modulate alpha1-AR reactivity in vascular smooth muscle and regulate 
      hemodynamics in normal and pathological conditions. Our observations point toward 
      CXCR4 and ACKR3 as new pharmacological targets to control vasoreactivity and 
      blood pressure.
FAU - Bach, Harold H 4th
AU  - Bach HH 4th
AD  - Department of Surgery, Loyola University Chicago, Maywood, Illinois, United 
      States of America Department of Molecular Pharmacology and Therapeutics, Loyola 
      University Chicago, Maywood, Illinois, United States of America.
FAU - Wong, Yee M
AU  - Wong YM
AD  - Department of Surgery, Loyola University Chicago, Maywood, Illinois, United 
      States of America.
FAU - Tripathi, Abhishek
AU  - Tripathi A
AD  - Department of Surgery, Loyola University Chicago, Maywood, Illinois, United 
      States of America.
FAU - Nevins, Amanda M
AU  - Nevins AM
AD  - Department of Biochemistry, Medical College of Wisconsin, Milwaukee, Wisconsin, 
      United States of America.
FAU - Gamelli, Richard L
AU  - Gamelli RL
AD  - Department of Surgery, Loyola University Chicago, Maywood, Illinois, United 
      States of America.
FAU - Volkman, Brian F
AU  - Volkman BF
AD  - Department of Biochemistry, Medical College of Wisconsin, Milwaukee, Wisconsin, 
      United States of America.
FAU - Byron, Kenneth L
AU  - Byron KL
AD  - Department of Molecular Pharmacology and Therapeutics, Loyola University Chicago, 
      Maywood, Illinois, United States of America.
FAU - Majetschak, Matthias
AU  - Majetschak M
AD  - Department of Surgery, Loyola University Chicago, Maywood, Illinois, United 
      States of America Department of Molecular Pharmacology and Therapeutics, Loyola 
      University Chicago, Maywood, Illinois, United States of America.
LA  - eng
GR  - R37 AI058072/AI/NIAID NIH HHS/United States
GR  - T32 GM008750/GM/NIGMS NIH HHS/United States
GR  - R01 GM107495/GM/NIGMS NIH HHS/United States
GR  - R01 AI058072/AI/NIAID NIH HHS/United States
GR  - T32GM008750/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20141013
PL  - England
TA  - Mol Med
JT  - Molecular medicine (Cambridge, Mass.)
JID - 9501023
RN  - 0 (Ackr3 protein, rat)
RN  - 0 (Adrenergic Agonists)
RN  - 0 (Benzylamines)
RN  - 0 (Chemokine CXCL12)
RN  - 0 (Cxcr4 protein, rat)
RN  - 0 (Cyclams)
RN  - 0 (Heterocyclic Compounds)
RN  - 0 (Ligands)
RN  - 0 (Oligopeptides)
RN  - 0 (Receptors, Adrenergic, alpha-1)
RN  - 0 (Receptors, CXCR)
RN  - 0 (Receptors, CXCR4)
RN  - 0 (TC14012)
RN  - 0 (Ubiquitin)
RN  - 1WS297W6MV (Phenylephrine)
RN  - S915P5499N (plerixafor)
SB  - IM
MH  - Adrenergic Agonists/pharmacology
MH  - Animals
MH  - Benzylamines
MH  - Blood Pressure/drug effects/physiology
MH  - Chemokine CXCL12/pharmacology
MH  - Cyclams
MH  - Heterocyclic Compounds/pharmacology
MH  - In Vitro Techniques
MH  - Ligands
MH  - Male
MH  - Mesenteric Arteries/drug effects/physiology
MH  - Myocytes, Cardiac/drug effects/physiology
MH  - Oligopeptides/pharmacology
MH  - Phenylephrine/pharmacology
MH  - Rats, Inbred Lew
MH  - Receptors, Adrenergic, alpha-1/*physiology
MH  - Receptors, CXCR/agonists/*physiology
MH  - Receptors, CXCR4/agonists/antagonists & inhibitors/*physiology
MH  - Shock, Hemorrhagic/physiopathology
MH  - Ubiquitin/pharmacology
MH  - Vasoconstriction/drug effects
MH  - Ventricular Function, Left/drug effects
PMC - PMC4212013
EDAT- 2014/07/18 06:00
MHDA- 2015/12/15 06:00
PMCR- 2014/10/13
CRDT- 2014/07/18 06:00
PHST- 2014/05/09 00:00 [received]
PHST- 2014/07/14 00:00 [accepted]
PHST- 2014/07/18 06:00 [entrez]
PHST- 2014/07/18 06:00 [pubmed]
PHST- 2015/12/15 06:00 [medline]
PHST- 2014/10/13 00:00 [pmc-release]
AID - molmed.2014.00101 [pii]
AID - 14_101_bach [pii]
AID - 10.2119/molmed.2014.00101 [doi]
PST - epublish
SO  - Mol Med. 2014 Oct 13;20(1):435-47. doi: 10.2119/molmed.2014.00101.