PMID- 1334809
OWN - NLM
STAT- MEDLINE
DCOM- 19930125
LR  - 20191210
IS  - 0143-4160 (Print)
IS  - 0143-4160 (Linking)
VI  - 13
IP  - 9
DP  - 1992 Oct
TI  - Calcium influx evoked by Ca2+ store depletion in human platelets is more 
      susceptible to cytochrome P-450 inhibitors than receptor-mediated calcium entry.
PG  - 553-64
AB  - We have previously reported that a component of ADP-evoked Ca2+ entry in human 
      platelets appears to be promoted following the release of Ca2+ from intracellular 
      stores. Other agonists may employ a similar mechanism. Here we have further 
      investigated the relationship between the state of filling of the Ca2+ stores and 
      plasma membrane Ca2+ permeability in Fura-2-loaded human platelets. Ca2+ influx 
      was promoted following store depletion by inhibitors of the endoplasmic reticulum 
      Ca(2+)-ATPase, thapsigargin (TG) and 2,5-di-(t-butyl)-1,4-benzohydroquinone 
      (tBuBHQ). Divalent cation entry was confirmed by quenching of Fura-2 fluorescence 
      with externally added Mn2+. It has been suggested that cytochrome P-450 may 
      couple Ca2+ store depletion to an increased plasma membrane Ca2+ permeability. In 
      apparent agreement with this, Mn2+ influx promoted by TG and tBuBHQ, or by 
      preincubation of cells in Ca(2+)-free medium, was inhibited by the imidazole 
      antimycotics, econazole and miconazole, which inhibit cytochrome P-450 activity. 
      Agonist-evoked Mn2+ influx was only partially inhibited by these compounds at the 
      same concentration (3 microM). Econazole (3 microM) reduced the Mn2+ quench 
      evoked by ADP by 38% of the control value and that evoked by vasopressin, 
      platelet activating factor (PAF) and thrombin no more than 15% of control, 20 s 
      after agonist addition. Stopped-flow fluorimetry indicated that econazole had no 
      detectable effect on the early time course of agonist-evoked Mn2+ entry or rises 
      in [Ca2+]i. These data confirm the existence of a Ca2+ entry pathway in human 
      platelets which is activated by depletion of the intracellular Ca2+ stores. 
      Further, the results support the suggestion that cytochrome P-450 may participate 
      in such a pathway. However, any physiological role for the cytochrome or its 
      products in agonist-evoked events appears to be in the long-term maintenance or 
      restoration of store Ca2+ content, rather than in promoting Ca2+ influx in the 
      initial stages of platelet Ca2+ signal generation.
FAU - Sargeant, P
AU  - Sargeant P
AD  - Physiological Laboratory, University of Cambridge, UK.
FAU - Clarkson, W D
AU  - Clarkson WD
FAU - Sage, S O
AU  - Sage SO
FAU - Heemskerk, J W
AU  - Heemskerk JW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Cell Calcium
JT  - Cell calcium
JID - 8006226
RN  - 0 (Calcium Channels)
RN  - 0 (Cytochrome P-450 Enzyme Inhibitors)
RN  - 0 (Hydroquinones)
RN  - 0 (Platelet Activating Factor)
RN  - 0 (Receptors, Cholinergic)
RN  - 0 (Ryanodine Receptor Calcium Release Channel)
RN  - 0 (Terpenes)
RN  - 11000-17-2 (Vasopressins)
RN  - 26XK13B61B (2,5-di-tert-butylhydroquinone)
RN  - 42Z2K6ZL8P (Manganese)
RN  - 61D2G4IYVH (Adenosine Diphosphate)
RN  - 67526-95-8 (Thapsigargin)
RN  - 6Z1Y2V4A7M (Econazole)
RN  - 7NNO0D7S5M (Miconazole)
RN  - 85166-31-0 (Inositol 1,4,5-Trisphosphate)
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
RN  - EC 3.4.21.5 (Thrombin)
RN  - EC 7.2.2.10 (Calcium-Transporting ATPases)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Adenosine Diphosphate/pharmacology
MH  - Blood Platelets/drug effects/enzymology/*metabolism
MH  - Calcium/*metabolism
MH  - Calcium Channels/*drug effects/metabolism/physiology
MH  - Calcium-Transporting ATPases/antagonists & inhibitors
MH  - Cell Compartmentation
MH  - Cytochrome P-450 Enzyme Inhibitors
MH  - Cytochrome P-450 Enzyme System/*physiology
MH  - Econazole/pharmacology
MH  - Humans
MH  - Hydroquinones/pharmacology
MH  - Inositol 1,4,5-Trisphosphate/physiology
MH  - Intracellular Fluid/metabolism
MH  - Ion Channel Gating/*drug effects
MH  - Manganese/metabolism
MH  - Miconazole/pharmacology
MH  - Osmolar Concentration
MH  - Platelet Activating Factor/pharmacology
MH  - Platelet Activation/drug effects
MH  - Receptors, Cholinergic/physiology
MH  - Ryanodine Receptor Calcium Release Channel
MH  - Signal Transduction
MH  - Terpenes/pharmacology
MH  - Thapsigargin
MH  - Thrombin/pharmacology
MH  - Vasopressins/pharmacology
EDAT- 1992/10/01 00:00
MHDA- 1992/10/01 00:01
CRDT- 1992/10/01 00:00
PHST- 1992/10/01 00:00 [pubmed]
PHST- 1992/10/01 00:01 [medline]
PHST- 1992/10/01 00:00 [entrez]
AID - 0143-4160(92)90035-Q [pii]
AID - 10.1016/0143-4160(92)90035-q [doi]
PST - ppublish
SO  - Cell Calcium. 1992 Oct;13(9):553-64. doi: 10.1016/0143-4160(92)90035-q.