title: Melatonin elevates intracellular free calcium in human platelets by inositol 1,4,5-trisphosphate independent mechanism.
abstract: Several studies have indicated the existence of direct effects of melatonin on platelets. Here we show that, melatonin at high concentration is capable of significantly raising platelet intracellular calcium even in the absence of an agonist. The effect of melatonin on platelets was abolished by luzindole, a melatonin receptor blocker, and rotenone, while it was unaffected by cell-permeable antagonists of either inositol 1,4,5-trisphosphate (IP(3)) receptor, phospholipase C (PLC), or bafilomycin A1, which discharges acidic calcium stores. Melatonin-induced manganese entry provided evidence for activation of bivalent cation entry. Thus, our data suggest that melatonin evoked the elevation of platelet intracellular calcium through depletion of mitochondrial Ca(2+) stores and store-operated calcium entry (SOCE), while the action was independent of the PLC-IP(3) axis.
authors.affiliation: Department of Biochemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
authors.forename: Sharda
authors.initials: S
authors.lastname: Kumari
authors.forename: Debabrata
authors.initials: D
authors.lastname: Dash
mesh_terms: D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism; D018942:Macrolides / Q000494:pharmacology; D008550:Melatonin / Q000494:pharmacology*; D008928:Mitochondria / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects; D044094:Receptors, Melatonin / Q000037:antagonists & inhibitors; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology; D014363:Tryptamines / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018942:Macrolides; D044094:Receptors, Melatonin; D014363:Tryptamines; C057154:luzindole; D015544:Inositol 1,4,5-Trisphosphate; C040929:bafilomycin A1; D010738:Type C Phospholipases; D013917:Thrombin; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D008550:Melatonin; D002118:Calcium