Indomethacin, esculetin and nordihydroguaiaretic acid modify arachidonate biosynthesis in rat adrenocortical cells.
We have studied the duration of the ACTH inhibition effect on the incorporation and transformation of [1-14 C] eicosatrienoic acid, in isolated adrenocortical cells of normal rats. The effect of esculetin, indomethacin and nordihydroguaiaretic acid alone, or in the presence of ACTH or diBucAMP on arachidonate biosynthesis was also investigated. ACTH and diBucAMP produced a significant inhibition in arachidonic acid biosynthesis. The inhibition produced by ACTH on delta 5 desaturating activity was considered to be a short-term effect. Nordihydroguaiaretic acid and esculetin provoked a depression in the uptake of 20:3 (n-6) acid and an inhibition in the formation of 20:4 (n-6) acid by adrenocortical cells. This effect was potentiated when the cells were currently treated with either ACTH or diBucAMP. Indomethacin produced no changes in the uptake of 20:3 (n-6) acid, while induced an increment on delta 5 desaturation activity. This effect would indicate that, normally, the metabolites produced by the cyclooxygenase pathway would operate by depressing arachidonic acid biosynthesis. Considering the negative regulation of the delta 5 desaturase activity system produced by ACTH through cAMP, and the positive modulation inferred by the results obtained in this work, it is possible to assume that there are, at least, two mechanisms that take place on 20:4 (n-6) acid formation. These mechanisms seem to work independently from one another and they probably interact when effecting a bi-directional control.
de Gómez Dumm
N T
NT
Consejo Nacional de Investigaciones Científicas y Técnicas, Argentina, CONICET-UNLP, Facultad de Ciencias Médicas, La Plata, Argentina.
Mandon
E C
EC
D000302:Adrenal Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000096:biosynthesis*; D003994:Bucladesine / Q000378:metabolism; D003374:Coumarins / Q000378:metabolism* / Q000493:pharmacokinetics; D016861:Cyclooxygenase Inhibitors / Q000378:metabolism* / Q000493:pharmacokinetics; D005260:Female; D006027:Glycosides / Q000378:metabolism* / Q000493:pharmacokinetics; D007213:Indomethacin / Q000378:metabolism* / Q000493:pharmacokinetics; D009637:Masoprocol / Q000378:metabolism* / Q000493:pharmacokinetics; D011284:Pregnenolone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar
D003374:Coumarins; D016861:Cyclooxygenase Inhibitors; D006027:Glycosides; C081583:esculentin steroid; D016718:Arachidonic Acid; D003994:Bucladesine; D011284:Pregnenolone; D009637:Masoprocol; D000324:Adrenocorticotropic Hormone; D007213:Indomethacin