Effects of Trolox C and SIN-1 on arachidonic acid metabolism and on cyclic GMP formation in leukocytes.
The effects of Trolox C (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid), a vitamin E analogue, (60-900 microM) and SIN-1 (3-morpholino sydnonimine), a nitric oxide donor, (30-3000 microM) on arachidonic acid metabolism and on cyclic GMP formation in calcium ionophore A23187 (calcimycin)-stimulated human polymorphonuclear leukocytes were investigated. Trolox C elicited a dose dependent decrease in leukotriene B4 levels and increase in prostaglandin E2 levels but did not affect cyclic GMP levels. SIN-1 dose dependently inhibited leukotriene B4 and stimulated prostaglandin E2 and cyclic GMP formation. Dibutyryl cyclic GMP did not affect the formation of leukotriene B4 and prostaglandin E2. Trolox C (180 microM), which itself had no effect on cyclic GMP levels, enhanced the effect of SIN-1 (100 microM) on cyclic GMP levels more than 5-fold. The effects of SIN-1 on arachidonic acid metabolism seem to be independent of cyclic GMP and are probably due to nitric oxide. In this experimental model both Trolox C and SIN-1 have similar actions on the prostaglandin/leukotriene ratio, and Trolox C potentiates the SIN-1-induced increase in cyclic GMP levels.
Riutta
A
A
Department of Biomedical Sciences, University of Tampere, Finland.
Alanko
J
J
Mucha
I
I
Vapaatalo
H
H
D000975:Antioxidants / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D002499:Centrifugation, Density Gradient; D002839:Chromans / Q000494:pharmacology*; D006152:Cyclic GMP / Q000378:metabolism*; D003995:Dibutyryl Cyclic GMP / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006162:Guanylate Cyclase / Q000378:metabolism; D006801:Humans; D007975:Leukotriene B4 / Q000378:metabolism; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D011863:Radioimmunoassay; D014665:Vasodilator Agents / Q000494:pharmacology; D014810:Vitamin E / Q000031:analogs & derivatives
D000975:Antioxidants; D002839:Chromans; D014665:Vasodilator Agents; D014810:Vitamin E; D007975:Leukotriene B4; D016718:Arachidonic Acid; D003995:Dibutyryl Cyclic GMP; D000001:Calcimycin; C002385:linsidomine; D008981:Molsidomine; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D015232:Dinoprostone; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid