Barbiturates inhibit intracellular Ca2+ rise induced by thrombin in rat platelets.
The effects of a number of barbiturates (anesthetic as well as anticonvulsant) on thrombin-induced calcium mobilization were tested in rat platelets using the fluorescent Ca2+ probe Fura-2. All drugs, except barbituric acid and Na-barbital, inhibited the thrombin-induced intracellular Ca2+ rise. Both the uptake of extracellular Ca2+ and the release of calcium from intracellular organelles were affected but influx was inhibited more strongly and at lower concentrations of the drugs (e.g. IC50 of thiopental was 0.83 mM for influx and 1.2 mM for intracellular release). Inhibitory potencies of the various barbiturates were markedly different. Thiopental was the most and barbital the least potent inhibitor. The order of inhibitory potency of the drugs appeared generally to follow their lipid solubility and the order of their hypnotic efficiency, with hexobarbital as the most conspicuous exception. Therefore, barbiturate treatment of cells perturbs agonist-induced calcium mobilization. This effect may be partially linked to their previously reported inhibitory action on two kinases, protein kinase C and phosphatidylinositol 4-phosphate kinase [1, 2].
Deshmukh
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New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York.
Kuizon
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Brockerhoff
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D000818:Animals; D001463:Barbiturates / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000097:blood*; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016257:Fura-2 / Q000737:chemistry; D008297:Male; D051381:Rats; D012631:Secobarbital / Q000494:pharmacology; D013050:Spectrometry, Fluorescence; D013874:Thiopental / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology*
D001463:Barbiturates; D012631:Secobarbital; D013917:Thrombin; D013874:Thiopental; D002118:Calcium; D016257:Fura-2