In vivo effects of isatin on rat platelet eicosanoids.
To establish the possible influence of isatin (2,3-dioxo-indole) on the activity of platelets, the effects of isatin on platelet eicosanoid synthesis were studied in rats. Different doses (12.5-50 mg/kg) of isatin were injected intraperitoneally (i.p.) and the effects on the arachidonate cascade of isolated platelets were investigated. Cells were labeled with [(14)C]arachidonic acid, then the eicosanoids were separated with overpressure thin-layer chromatography and were quantitatively determined with a liquid scintillation analyzer. The lipoxygenase pathway was significantly inhibited by isatin (50 mg/kg) treatment and also the overall activity of the arachidonate cascade was diminished; however, the cyclooxygenase system was significantly stimulated. A 50-mg/kg i.p. dose of isatin significantly increased the production of vasoconstrictor cyclooxygenase metabolites. Among the vasodilator cyclooxygenase products, the synthesis of PGE2 and PGD2 were significantly decreased while that of 12-hydroxyheptadecatrienoic acid (HHT) increased upon isatin (50 mg/kg) administration. Our results provide further evidence on the peripheral actions of isatin and suggest that this endogenous indole may induce significant changes in the production of blood platelet arachidonic acid metabolites, which are important regulatory substances, thus isatin may potentially affect an even broader range of functions than was previously assumed.
Pataki
Imre
I
Department of Pathophysiology, Albert Szent-Györgyi Medical and Pharmaceutical Center, University of Szeged, MTA-SZTE Neurohumoral Research Group, Semmelweis u. 1., Pf., 427 H6701 Szeged, Hungary.
Mezei
Zsófia
Z
Adamik
Agnes
A
Glover
Vivette
V
Gecse
Arpád
A
Telegdy
Gyula
G
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002250:Carbon Radioisotopes; D015232:Dinoprostone / Q000096:biosynthesis; D015777:Eicosanoids / Q000032:analysis* / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000096:biosynthesis; D007510:Isatin / Q000008:administration & dosage / Q000494:pharmacology*; D008084:Lipoxygenase / Q000378:metabolism; D008297:Male; D015230:Prostaglandin D2 / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar
D002250:Carbon Radioisotopes; D015777:Eicosanoids; D005231:Fatty Acids, Unsaturated; D016718:Arachidonic Acid; C008033:12-hydroxy-5,8,10-heptadecatrienoic acid; D007510:Isatin; D008084:Lipoxygenase; D015232:Dinoprostone; D015230:Prostaglandin D2