Rapid inhibition by sodium azide of the phosphoinositide-mediated calcium response to serotonin stimulation in human platelets: preservation in Alzheimer's disease.
The effect of sodium azide (NaN(3)) upon platelet Ca(2+) signalling has been investigated. A 60 s preincubation with 1 mM NaN(3) reduced the Ca(2+) response to 1 microM serotonin without a corresponding reduction in the responses to 52 mU/ml thrombin or 70 microM beta-amyloid(25-35) (A beta(25-35)). The effect of NaN(3) upon the response to serotonin, which was not blocked by either glutathione ethyl ester (GTEE) or dithiothreitol (DTT), was similar in platelets obtained from patients with Alzheimer's disease and from age- and gender-matched controls. After a preincubation time of 5 min was used, the Ca(2+) response to thrombin was greatly reduced by 1 mM NaN(3), but not by 50 microM 4-hydroxynonenal (HNE, 50 microM). Platelet levels of HNE and malondialdehyde were not significantly affected by up to 30 min of incubation with NaN(3) at room temperature. It is concluded that the rapid effect of NaN(3) upon the Ca(2+) response to serotonin in human platelets is not mediated by an inhibition of cytochrome c oxidase, and is due to an action proximal to phosphoinositide-specific phospholipase C.
Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, SE-901 87, Sweden. Henrieeta.Hedin@pharm.umu.se
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Hedin
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Eriksson
C J
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Fowler
D000328:Adult; D000368:Aged; D000447:Aldehydes / Q000378:metabolism; D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000494:pharmacology; D000704:Analysis of Variance; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008875:Middle Aged; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology*; D019810:Sodium Azide / Q000494:pharmacology*; D013917:Thrombin / Q000378:metabolism / Q000494:pharmacology
D000447:Aldehydes; D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D010716:Phosphatidylinositols; C074636:amyloid beta-protein (25-35); D012701:Serotonin; D008315:Malondialdehyde; D019810:Sodium Azide; D013917:Thrombin; C027576:4-hydroxy-2-nonenal