PMID- 12086980
OWN - NLM
STAT- MEDLINE
DCOM- 20021223
LR  - 20181113
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 136
IP  - 5
DP  - 2002 Jul
TI  - The extracellular regulated kinases (ERK) 1/2 mediate cannabinoid-induced 
      inhibition of gap junctional communication in endothelial cells.
PG  - 709-16
AB  - 1. Cannabinoids are potent inhibitors of endothelium-derived hyperpolarizing 
      factor (EDHF)-mediated relaxations. We set out to study the mechanism underlying 
      this effect and the possible role of cannabinoid-induced changes in intercellular 
      gap junction communication. 2. In cultured endothelial cells, 
      Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and the cannabinoid receptor agonist 
      HU210, increased the phosphorylation of extracellular regulated kinases 1/2 
      (ERK1/2) and inhibited gap junctional communication, as determined by Lucifer 
      Yellow dye transfer and electrical capacity measurements. 3. Delta(9)-THC 
      elicited a pronounced increase in the phosphorylation of connexin 43, which was 
      sensitive to PD98059 and U0126, two inhibitors of ERK1/2 activation. Inhibition 
      of ERK1/2 also prevented the Delta(9)-THC-induced inhibition of gap junctional 
      communication. 4. Delta(9)-THC prevented both the bradykinin-induced 
      hyperpolarization and the nitric oxide and prostacyclin-independent relaxation of 
      pre-contracted rings of porcine coronary artery. These effects were prevented by 
      PD98059 as well as U0126. 5. In the absence of Delta(9)-THC, neither PD98059 nor 
      U0126 affected the NO-mediated relaxation of coronary artery rings but both 
      substances induced a leftward shift in the concentration - relaxation curve to 
      bradykinin when diclofenac and N(omega)nitro-L-arginine were present. Moreover, 
      PD98059 and U0126 prolonged the bradykinin-induced hyperpolarization of porcine 
      coronary arteries, without affecting the magnitude of the response. 6. These 
      results indicate that the cannabinoid-induced activation of ERK1/2, which leads 
      to the phosphorylation of connexin 43 and inhibition of gap junctional 
      communication, may partially account for the Delta(9)-THC-induced inhibition of 
      EDHF-mediated relaxation. Moreover, the activation of ERK1/2 by endothelial cell 
      agonists such as bradykinin, appears to exert a negative feedback inhibition on 
      EDHF-mediated responses.
FAU - Brandes, R P
AU  - Brandes RP
AD  - Institut fur Kardiovaskulare Physiologie, Klinikum der J.W. Goethe-Universitat, 
      Theodor-Stern-Kai-7, 60596 Frankfurt am Main, Germany. 
      R.Brandes@em.uni-frankfurt.de
FAU - Popp, R
AU  - Popp R
FAU - Ott, G
AU  - Ott G
FAU - Bredenkotter, D
AU  - Bredenkotter D
FAU - Wallner, C
AU  - Wallner C
FAU - Busse, R
AU  - Busse R
FAU - Fleming, I
AU  - Fleming I
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Biological Factors)
RN  - 0 (Cannabinoids)
RN  - 0 (endothelium-dependent hyperpolarization factor)
RN  - 7J8897W37S (Dronabinol)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - R6VT8U5372 (HU 211)
SB  - IM
MH  - Animals
MH  - Biological Factors/metabolism
MH  - Cannabinoids/*pharmacology
MH  - Dronabinol/*analogs & derivatives/pharmacology
MH  - Endothelium, Vascular/*drug effects/enzymology
MH  - Gap Junctions/*drug effects/enzymology
MH  - Humans
MH  - In Vitro Techniques
MH  - Mitogen-Activated Protein Kinase 1/*metabolism
MH  - Mitogen-Activated Protein Kinase 3
MH  - Mitogen-Activated Protein Kinases/*metabolism
MH  - Neural Inhibition/drug effects/physiology
MH  - Swine
PMC - PMC1573402
EDAT- 2002/06/28 10:00
MHDA- 2002/12/27 04:00
PMCR- 2003/07/01
CRDT- 2002/06/28 10:00
PHST- 2002/06/28 10:00 [pubmed]
PHST- 2002/12/27 04:00 [medline]
PHST- 2002/06/28 10:00 [entrez]
PHST- 2003/07/01 00:00 [pmc-release]
AID - 0704776 [pii]
AID - 10.1038/sj.bjp.0704776 [doi]
PST - ppublish
SO  - Br J Pharmacol. 2002 Jul;136(5):709-16. doi: 10.1038/sj.bjp.0704776.