PMID- 17095584
OWN - NLM
STAT- MEDLINE
DCOM- 20070301
LR  - 20231213
IS  - 0026-895X (Print)
IS  - 0026-895X (Linking)
VI  - 71
IP  - 2
DP  - 2007 Feb
TI  - 2-aminoethoxydiphenyl borate directly inhibits channels composed of connexin26 
      and/or connexin32.
PG  - 570-9
AB  - 2-aminoethoxydiphenyl borate (2-APB), a commonly used blocker of IP3-induced 
      calcium ion release and of store-operated channels, inhibits gap junction 
      conductance when applied to cultured cells. The character and pharmacology of 
      this inhibition was explored using 1) hemichannels composed of connexin32 (Cx32) 
      and/or connexin26 (Cx26) purified from native sources and from transfected HeLa 
      cells in which the connexin had a cleavable C-terminal epitope tag and 2) the 
      corresponding junctional channels. Using reconstituted hemichannels in a 
      liposome-based transport-specific fractionation assay (TSF), 2-APB reversibly 
      inhibited homomeric Cx32 and heteromeric Cx26/Cx32 channels from native tissue 
      and their tagged forms from HeLa cells. The IC50-TSF value of the inhibition was 
      approximately 47 microM at pH 6.5. 2-APB did not inhibit tagged homomeric Cx26 
      channels even after tag cleavage (leaving several amino acids at the carboxyl 
      terminus). Protonated 2-APB is the inhibitory agent, but channel sensitivity to 
      2-APB also increases as pH is lowered. To help define the chemical requirements 
      for inhibition, the effects of four structural analogs of 2-APB were determined. 
      The inhibitory action of 2-APB was shown to be distinct from that of 
      aminosulfonates. 2-APB and its analogs, except phenytoin, inhibited dye-coupling 
      through junctional channels formed by all the tagged channel forms except Cx26, 
      consistent with the TSF studies. However 2-APB significantly inhibited dye 
      coupling between cells expressing untagged Cx26, suggesting that an unmodified C 
      terminus is required for action on Cx26 channels. These results show that 
      protonated 2-APB directly and reversibly inhibits connexin channels composed of 
      Cx26 and/or Cx32 and suggest involvement of the carboxyl-terminal domain.
FAU - Tao, Liang
AU  - Tao L
AD  - Department of Pharmacology, Zhongsan College of Medicine, Sun Yet-San University, 
      Guangzhou China 510080. taol@mail.sysu.edu.cn
FAU - Harris, Andrew L
AU  - Harris AL
LA  - eng
GR  - GM36044/GM/NIGMS NIH HHS/United States
GR  - GM61406/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20061109
PL  - United States
TA  - Mol Pharmacol
JT  - Molecular pharmacology
JID - 0035623
RN  - 0 (Boron Compounds)
RN  - 0 (Connexins)
RN  - 0 (GJB2 protein, human)
RN  - 0 (Ion Channels)
RN  - 0 (Liposomes)
RN  - 127120-53-0 (Connexin 26)
RN  - E4ES684O93 (2-aminoethoxydiphenyl borate)
SB  - IM
MH  - Boron Compounds/chemistry/*pharmacology
MH  - Connexin 26
MH  - *Connexins/genetics
MH  - HeLa Cells
MH  - Humans
MH  - Hydrogen-Ion Concentration
MH  - Inhibitory Concentration 50
MH  - Intercellular Junctions
MH  - Ion Channels/*antagonists & inhibitors
MH  - Liposomes
MH  - Structure-Activity Relationship
MH  - Transfection
MH  - Gap Junction beta-1 Protein
EDAT- 2006/11/11 09:00
MHDA- 2007/03/03 09:00
CRDT- 2006/11/11 09:00
PHST- 2006/11/11 09:00 [pubmed]
PHST- 2007/03/03 09:00 [medline]
PHST- 2006/11/11 09:00 [entrez]
AID - mol.106.027508 [pii]
AID - 10.1124/mol.106.027508 [doi]
PST - ppublish
SO  - Mol Pharmacol. 2007 Feb;71(2):570-9. doi: 10.1124/mol.106.027508. Epub 2006 Nov 
      9.