PMID- 18068335
OWN - NLM
STAT- MEDLINE
DCOM- 20080414
LR  - 20190412
IS  - 0898-6568 (Print)
IS  - 0898-6568 (Linking)
VI  - 20
IP  - 2
DP  - 2008 Feb
TI  - SERCA2b and 3 play a regulatory role in store-operated calcium entry in human 
      platelets.
PG  - 337-46
AB  - Two agonist-releasable Ca(2+)stores have been identified in human platelets 
      differentiated by the distinct sensitivity of their SERCA isoforms to 
      thapsigargin (TG) and 2,5-di-(tert-butyl)-1,4-hydroquinone (TBHQ). Here we have 
      examined whether the SERCA isotypes might be involved in store-operated 
      Ca(2+)entry (SOCE) activated by the physiological agonist thrombin in human 
      platelets. Ca(2+)-influx evoked by thrombin (0.01 U/mL) reached a maximum after 3 
      min, which was consistent with the decrease in the Ca(2+)content in the stores; 
      afterwards, the extent of SOCE decreased with no correlation with the 
      accumulation of Ca(2+)in the stores. Inhibition of SERCA2b, by 10 nM TG, and 
      SERCA3, with 20 microM TBHQ, individually or simultaneously, accelerated Ca(2+) 
      store discharge and subsequently enhanced the extent of SOCE stimulated by 
      thrombin. In addition, TG and TBHQ modified the time course of thrombin-evoked 
      SOCE from a transient to a sustained increase in Ca(2+) influx, which reveals a 
      negative role for SERCAs in the regulation of SOCE. This effect was consistent 
      under conditions that inhibit Ca(2+) extrusion by PMCA or the Na(+)/Ca(2+) 
      exchanger. Coimmunoprecipitation experiments revealed that thrombin stimulates 
      direct interaction between SERCA2b and 3 with the hTRPC1 channel, an effect that 
      was found to be independent of SERCA activity. In summary, our results suggest 
      that SERCA2b and 3 modulate thrombin-stimulated SOCE probably by direct 
      interaction with the hTRPC1 channel in human platelets.
FAU - Redondo, Pedro C
AU  - Redondo PC
AD  - Department of Physiology, Development and Neuroscience of University of 
      Cambridge, Cambridge, CB3 9ET, United Kingdom. pcr@unex.es
FAU - Salido, Gines M
AU  - Salido GM
FAU - Pariente, Jose A
AU  - Pariente JA
FAU - Sage, Stewart O
AU  - Sage SO
FAU - Rosado, Juan A
AU  - Rosado JA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20071026
PL  - England
TA  - Cell Signal
JT  - Cellular signalling
JID - 8904683
RN  - 0 (Inositol 1,4,5-Trisphosphate Receptors)
RN  - 0 (Isoenzymes)
RN  - 0 (TRPC Cation Channels)
RN  - 0 (transient receptor potential cation channel, subfamily C, member 1)
RN  - EC 3.4.21.5 (Thrombin)
RN  - EC 3.6.3.8 (Sarcoplasmic Reticulum Calcium-Transporting ATPases)
RN  - EC 7.2.2.10 (ATP2A2 protein, human)
RN  - EC 7.2.2.10 (ATP2A3 protein, human)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Blood Platelets/drug effects/*enzymology
MH  - Calcium/metabolism
MH  - *Calcium Signaling/drug effects
MH  - Humans
MH  - Immunoprecipitation
MH  - Inositol 1,4,5-Trisphosphate Receptors/metabolism
MH  - Isoenzymes/metabolism
MH  - Protein Binding/drug effects
MH  - Sarcoplasmic Reticulum Calcium-Transporting ATPases/antagonists & 
      inhibitors/*metabolism
MH  - TRPC Cation Channels/metabolism
MH  - Thrombin/pharmacology
MH  - Time Factors
EDAT- 2007/12/11 09:00
MHDA- 2008/04/15 09:00
CRDT- 2007/12/11 09:00
PHST- 2007/09/10 00:00 [received]
PHST- 2007/10/18 00:00 [accepted]
PHST- 2007/12/11 09:00 [pubmed]
PHST- 2008/04/15 09:00 [medline]
PHST- 2007/12/11 09:00 [entrez]
AID - S0898-6568(07)00323-3 [pii]
AID - 10.1016/j.cellsig.2007.10.019 [doi]
PST - ppublish
SO  - Cell Signal. 2008 Feb;20(2):337-46. doi: 10.1016/j.cellsig.2007.10.019. Epub 2007 
      Oct 26.