Two pathways for store-mediated calcium entry in human platelets.
In human platelets and other non-excitable cell types depletion of the intracellular calcium stores promotes calcium entry across the plasma membrane. Although the mechanism of this store-mediated calcium entry remains uncertain, it has been suggested that a tyrosine phosphorylation step could be involved. In support of this hypothesis various tyrosine kinase inhibitors have been shown to reduce store-mediated calcium entry in platelets, although this inhibition is never complete. Here we investigate the properties of store-mediated calcium entry in human platelets during the time course of its activation. Our data suggest that at least two pathways may contribute to store-mediated calcium entry in these cells. An early component, activated soon after the initiation of Ca2+ store depletion, is insensitive to trivalent cations, SKF 96365 and tyrosine kinase inhibitors. This is followed by a second component which is inhibited by La3+, SKF 96365 and by tyrosine kinase inhibitors. These results suggest a role for tyrosine kinases in generating only the later stages of store-mediated calcium entry in platelets and may explain the incomplete inhibition of this pathway by inhibitors of tyrosine kinases.
Department of Physiology, University of Cambridge, UK. sj10014@cus.cam.ac.uk
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Jenner
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D000730:Androstadienes / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D001792:Blood Platelets / Q000737:chemistry / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D002614:Chelating Agents / Q000494:pharmacology; D004464:Econazole / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D004791:Enzyme Inhibitors; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D007811:Lanthanum / Q000494:pharmacology; D008345:Manganese / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D019284:Thapsigargin / Q000494:pharmacology; D014443:Tyrosine / Q000378:metabolism; D000077191:Wortmannin
D000730:Androstadienes; D002121:Calcium Channel Blockers; D002614:Chelating Agents; D004791:Enzyme Inhibitors; D007093:Imidazoles; D007476:Ionophores; C028521:lanthanum chloride; D014443:Tyrosine; D008345:Manganese; D004533:Egtazic Acid; D015759:Ionomycin; D019284:Thapsigargin; D007811:Lanthanum; D004464:Econazole; D011505:Protein-Tyrosine Kinases; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D002118:Calcium; D000077191:Wortmannin