PMID- 11742538
OWN - NLM
STAT- MEDLINE
DCOM- 20020219
LR  - 20190501
IS  - 0264-6021 (Print)
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Linking)
VI  - 361
IP  - Pt 1
DP  - 2002 Jan 1
TI  - Adenophostin A and ribophostin, but not inositol 1,4,5-trisphosphate or 
      manno-adenophostin, activate the Ca2+ release-activated Ca2+ current, I(CRAC), in 
      weak intracellular Ca2+ buffer.
PG  - 133-41
AB  - Under physiological conditions of weak intracellular Ca(2+) buffering (0.1 mM 
      EGTA), the second messenger Ins(1,4,5)P(3) often fails to activate any detectable 
      store-operated Ca(2+) current. However, it has been reported that the fungal 
      metabolite adenophostin A [which has a severalfold higher affinity than 
      Ins(1,4,5)P(3) for Ins(1,4,5)P(3) receptors] consistently activates the current 
      under similar conditions. Here, whole-cell patch clamp experiments have been 
      performed to examine how adenophostin A can activate the store-operated Ca(2+) 
      current (I(CRAC)) in RBL-1 (rat basophilic leukaemia) cells. In a strong 
      intracellular Ca(2+) buffer, saturating concentrations of adenophostin A 
      activated I(CRAC) maximally and the current amplitude and kinetics were 
      indistinguishable from those obtained with high concentrations of Ins(1,4,5)P(3). 
      In a weak Ca(2+) buffer, adenophostin A consistently activated I(CRAC), but the 
      current was submaximal. High concentrations of Ins(1,4,5)P(3) or the 
      non-metabolizable analogue Ins(2,4,5)P(3) were largely ineffective under these 
      conditions. The size of I(CRAC) to adenophostin A in weak Ca(2+) buffer could be 
      significantly increased by either inhibiting sarcoplasmic/endoplasmic-reticulum 
      Ca(2+)-ATPase ('SERCA') pumps with thapsi-gargin or enhancing mitochondrial 
      Ca(2+) uptake, although blocking the mitochondrial Ca(2+) uniporter with 
      Ruthenium Red did not suppress the activation of the current. Changing the levels 
      of free ATP in the recording pipette did not enhance the size of I(CRAC) evoked 
      by adenophostin A. We also examined two structurally distinct analogues of 
      adenophostin A (manno-adenophostin and ribophostin), for which the affinities for 
      the Ins(1,4,5)P(3) receptor are similar to that of Ins(1,4,5)P(3) in equilibrium 
      binding experiments. Although these analogues were able to activate I(CRAC) to 
      its maximal extent in strong buffer, ribophostin, but not manno-adenophostin, 
      consistently activated the current in weak buffer. We conclude that adenophostin 
      A and ribophostin are able to activate I(CRAC) in weak buffer through a mechanism 
      that is quite distinct from that employed by Ins(1,4,5)P(3) and 
      manno-adenophostin and is not related to equilibrium affinities.
FAU - Parekh, Anant B
AU  - Parekh AB
AD  - Laboratory of Molecular and Cellular Signalling, Department of Physiology, 
      University of Oxford, Parks Road, Oxford OX1 3PT, U.K. 
      anant.parekh@physiol.ox.ac.uk
FAU - Riley, Andrew M
AU  - Riley AM
FAU - Potter, Barry V L
AU  - Potter BV
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (Buffers)
RN  - 0 (Calcium Channel Agonists)
RN  - 0 (Calcium Channels)
RN  - 0 (Disaccharides)
RN  - 0 (Inositol Phosphates)
RN  - 0 (Sugar Phosphates)
RN  - 0 (manno-adenophostin)
RN  - 0 (ribophostin)
RN  - 149091-92-9 (adenophostin A)
RN  - 85166-31-0 (Inositol 1,4,5-Trisphosphate)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - 91840-07-2 (inositol 2,4,5-trisphosphate)
RN  - K72T3FS567 (Adenosine)
SB  - IM
MH  - Adenosine/*analogs & derivatives/*pharmacology
MH  - Adenosine Triphosphate/pharmacology
MH  - Animals
MH  - Buffers
MH  - Calcium Channel Agonists/*pharmacology
MH  - Calcium Channels/drug effects/metabolism
MH  - Calcium Signaling/*drug effects
MH  - Disaccharides/*pharmacology
MH  - Inositol 1,4,5-Trisphosphate/*pharmacology
MH  - Inositol Phosphates/pharmacology
MH  - Intracellular Fluid/drug effects/metabolism
MH  - Mitochondria/drug effects/metabolism
MH  - Patch-Clamp Techniques
MH  - Rats
MH  - Sugar Phosphates/*pharmacology
MH  - Tumor Cells, Cultured
PMC - PMC1222288
EDAT- 2001/12/18 10:00
MHDA- 2002/02/20 10:01
PMCR- 2002/07/01
CRDT- 2001/12/18 10:00
PHST- 2001/12/18 10:00 [pubmed]
PHST- 2002/02/20 10:01 [medline]
PHST- 2001/12/18 10:00 [entrez]
PHST- 2002/07/01 00:00 [pmc-release]
AID - 10.1042/0264-6021:3610133 [doi]
PST - ppublish
SO  - Biochem J. 2002 Jan 1;361(Pt 1):133-41. doi: 10.1042/0264-6021:3610133.