PMID- 10220561
OWN - NLM
STAT- MEDLINE
DCOM- 19990601
LR  - 20171213
IS  - 0026-895X (Print)
IS  - 0026-895X (Linking)
VI  - 55
IP  - 5
DP  - 1999 May
TI  - ATP-Sensitive K+ channel modulator binding to sulfonylurea receptors SUR2A and 
      SUR2B: opposite effects of MgADP.
PG  - 832-40
AB  - KATP channels are heteromeric complexes of inwardly rectifying K+ channel 
      subunits and sulfonylurea receptors (SURs). SUR2A and SUR2B, which differ within 
      the carboxyl terminal exon 38, are characteristic for the cardiac and smooth 
      muscle type channels, respectively. Here we compare binding of the tritiated KATP 
      channel opener, [3H]P1075, to membranes from human embryonic kidney (HEK) cells 
      transfected with murine SUR2A and 2B at 37 degrees C. Binding to both SURs 
      required addition of Mg2+ and ATP in the low micromolar range. In the presence of 
      MgATP, micromolar concentrations of MgADP, formed by the ATPase activity of the 
      membrane preparation, increased binding to SUR2A but inhibited binding to SUR2B. 
      Decreasing temperatures strongly reduced [3H]P1075 binding to SUR2A, whereas 
      binding to SUR2B was increased in a bell-shaped manner. Kinetic experiments 
      revealed a faster dissociation of the [3H]P1075-SUR2A complex, whereas the 
      association rate constants for [3H]P1075 binding to SUR2A and 2B were similar. 
      Openers inhibited [3H]P1075 binding to SUR2A with potencies approximately 4 times 
      lower than to SUR2B; in contrast, glibenclamide inhibited [3H]P1075 binding to 
      SUR2A approximately 8 times more potently than to SUR2B. The data suggest that 
      SUR2A and 2B represent the opener receptors of cardiac and vascular smooth muscle 
      KATP channels, respectively, and show that MgADP is an important modulator of 
      opener binding to SUR. The different carboxyl termini of SUR2A and 2B lead to 
      differences in the MgADP dependence and the thermodynamics of [3H]P1075 binding, 
      as well as in the affinities for openers and glibenclamide, underlining the 
      importance of this part of the molecule for KATP channel modulator binding.
FAU - Hambrock, A
AU  - Hambrock A
AD  - Department of Pharmacology, University of Tubingen, Tubingen, Germany.
FAU - Loffler-Walz, C
AU  - Loffler-Walz C
FAU - Kloor, D
AU  - Kloor D
FAU - Delabar, U
AU  - Delabar U
FAU - Horio, Y
AU  - Horio Y
FAU - Kurachi, Y
AU  - Kurachi Y
FAU - Quast, U
AU  - Quast U
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Pharmacol
JT  - Molecular pharmacology
JID - 0035623
RN  - 0 (ABCC9 protein, human)
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (Abcc9 protein, mouse)
RN  - 0 (Guanidines)
RN  - 0 (KATP Channels)
RN  - 0 (Potassium Channels)
RN  - 0 (Potassium Channels, Inwardly Rectifying)
RN  - 0 (Pyridines)
RN  - 0 (Receptors, Drug)
RN  - 0 (Sulfonylurea Receptors)
RN  - 0 (uK-ATP-1 potassium channel)
RN  - 60559-98-0 (N-cyano-N'-(1,1-dimethylpropyl)-N''-(3-pyridinyl)guanidine)
RN  - 61D2G4IYVH (Adenosine Diphosphate)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - I38ZP9992A (Magnesium)
SB  - IM
MH  - *ATP-Binding Cassette Transporters
MH  - Adenosine Diphosphate/*metabolism/pharmacology
MH  - Adenosine Triphosphate/metabolism
MH  - Animals
MH  - Cell Membrane/drug effects/metabolism
MH  - Cells, Cultured
MH  - Guanidines/*pharmacology
MH  - Humans
MH  - KATP Channels
MH  - Kinetics
MH  - Magnesium/metabolism
MH  - Mice
MH  - Potassium Channels/drug effects/*metabolism
MH  - *Potassium Channels, Inwardly Rectifying
MH  - Pyridines/*pharmacology
MH  - Receptors, Drug/drug effects/*metabolism
MH  - Sulfonylurea Receptors
MH  - Temperature
MH  - Transfection
EDAT- 1999/04/30 00:00
MHDA- 1999/04/30 00:01
CRDT- 1999/04/30 00:00
PHST- 1999/04/30 00:00 [pubmed]
PHST- 1999/04/30 00:01 [medline]
PHST- 1999/04/30 00:00 [entrez]
PST - ppublish
SO  - Mol Pharmacol. 1999 May;55(5):832-40.