PMID- 15748704
OWN - NLM
STAT- MEDLINE
DCOM- 20050412
LR  - 20070718
IS  - 0006-2952 (Print)
IS  - 0006-2952 (Linking)
VI  - 69
IP  - 6
DP  - 2005 Mar 15
TI  - Suppression of Ca2+ influx by unfractionated heparin in non-excitable intact 
      cells via multiple mechanisms.
PG  - 929-40
AB  - Effect of unfractionated heparin (UFH), described as a cell-impermeant IP3 
      receptor antagonist, was studied on the capacitive Ca(2+) entry in 
      non-permeabilized, intact cells, measuring the intracellular Ca(2+) levels using 
      fluorescence microplate technique. Ca(2+) influx induced via Ca(2+) mobilization 
      by histamine in Hela cells or evoked by store depletion with thapsigargin in 
      RBL-2H3 cells was dose-dependently suppressed by UFH added either before or after 
      the stimuli. UFH also prevented the spontaneous Ba(2+) entry indicating that the 
      non-capacitive Ca(2+) channels may also be affected. In addition, UFH caused a 
      significant and dose-dependent delay in Ca(2+), and other bivalent cation inflow 
      after treatment of the cells with Triton X-100, but it did not diminish the 
      amount of these cations indicating that UFH did not act simply as a cation 
      chelator, but modulated the capacitive Ca(2+) entry possibly via store operated 
      Ca(2+) channels (SOCCs). Inhibitory activities of UFH and 2-aminoethyl diphenyl 
      borate on the capacitive Ca(2+) influx was found reversible, but the time courses 
      of their actions were dissimilar suggesting distinct modes of action. It was also 
      demonstrated using a fluorescence potentiometric dye that UFH had a considerable 
      hyperpolarizing effect and could alter the changes of membrane potential during 
      Ca(2+) influx after store depletion by thapsigargin. We presume that the 
      hyperpolarizing property of this agent might contribute to the suppression of 
      Ca(2+) influx. We concluded that UFH can negatively modulate SOCCs and also other 
      non-capacitive Ca(2+) channels and these activities might also account for its 
      multiple biological effects.
FAU - Nemeth, Klara
AU  - Nemeth K
AD  - Department of Immunopharmacology, IVAX Drug Research Institute, 47-49 Berlini 
      utca, H-1045 Budapest, Hungary. klara.nemeth@idri.hu <klara.nemeth@idri.hu>
FAU - Kurucz, Istvan
AU  - Kurucz I
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Calcium Channels)
RN  - 0 (ITPR1 protein, human)
RN  - 0 (Inositol 1,4,5-Trisphosphate Receptors)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 9005-49-6 (Heparin)
SB  - IM
MH  - Animals
MH  - Calcium Channels/metabolism
MH  - Calcium Signaling/*drug effects/physiology
MH  - Cell Membrane/*drug effects/metabolism
MH  - HeLa Cells
MH  - Heparin/*pharmacology
MH  - Humans
MH  - Inositol 1,4,5-Trisphosphate Receptors
MH  - Membrane Potentials/drug effects/physiology
MH  - Rats
MH  - Receptors, Cytoplasmic and Nuclear/metabolism
EDAT- 2005/03/08 09:00
MHDA- 2005/04/13 09:00
CRDT- 2005/03/08 09:00
PHST- 2004/09/23 00:00 [received]
PHST- 2004/12/09 00:00 [accepted]
PHST- 2005/03/08 09:00 [pubmed]
PHST- 2005/04/13 09:00 [medline]
PHST- 2005/03/08 09:00 [entrez]
AID - S0006-2952(04)00822-6 [pii]
AID - 10.1016/j.bcp.2004.12.006 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2005 Mar 15;69(6):929-40. doi: 10.1016/j.bcp.2004.12.006.