Investigation into the rapid effects of 17 beta-estradiol and neuroactive steroids upon beta-amyloid(25-35)-induced activation of phosphoinositide-specific phospholipase C in human platelets.
In the present study, the rapid effects of five steroids (17 beta-estradiol, progesterone, allopregnanolone, 3 alpha-hydroxy-5 alpha-pregnan-20-one and 3 alpha-hydroxy-5 beta-pregnan-20-one) and the plant steroid trans-resveratrol upon the calcium response to beta-amyloid(25-35) peptide (A beta(25-35)) in human platelets was measured. A beta(25-35) produced a robust increase in intracellular calcium due to a direct activation of phosphoinositide-specific phospholipase C. None of the steroids significantly affected the response to A beta(25-35). In contrast, trans-resveratrol appeared to increase the response to A beta(25-35) at a concentration that decreased the response to thrombin, although the possibility that these changes are artifactual could not be ruled out. It is concluded that although steroids affect human platelet Ca2+ homeostasis, this is not a rapid event, unless very high concentrations are used.
Jonsson
K O
KO
Department of Pharmacology and Clinical Neurosciences, Umeå University, Umeå, Sweden. Kentolov.Jonsson@pharm.umu.se
Hedin
H L
HL
Fowler
C J
CJ
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology*; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D006490:Hemostatics / Q000494:pharmacology; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D010446:Peptide Fragments / Q000494:pharmacology*; D054801:Phosphoinositide Phospholipase C; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011280:Pregnanolone / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology; D000077185:Resveratrol; D012701:Serotonin / Q000494:pharmacology; D013050:Spectrometry, Fluorescence; D013256:Steroids / Q000494:pharmacology*; D013267:Stilbenes / Q000494:pharmacology*; D013917:Thrombin / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D004968:Estrogens, Non-Steroidal; D006490:Hemostatics; D010446:Peptide Fragments; D010975:Platelet Aggregation Inhibitors; D013256:Steroids; D013267:Stilbenes; C074636:amyloid beta-protein (25-35); D012701:Serotonin; D011374:Progesterone; D004958:Estradiol; D011280:Pregnanolone; D010727:Phosphoric Diester Hydrolases; D054801:Phosphoinositide Phospholipase C; D013917:Thrombin; D000077185:Resveratrol; D002118:Calcium