S-adenosyl-L-methionine reverses the cholestatic effect of ethinylestradiol in rat hepatocytes by increasing its catabolism
✍ Scribed by Amparo Larrauri; José V. Castell; Guillermo Garrido; Joaquín Berenguer; M. José Gómez-lechón
- Publisher
- Springer
- Year
- 1992
- Tongue
- English
- Weight
- 807 KB
- Volume
- 8
- Category
- Article
- ISSN
- 0742-2091
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✦ Synopsis
In this study, ethinylestradiol inhibited the uptake of taurocholate by cultured rat hepatocytes, increasing the Krn while leaving the Vmax unchanged. S-Adenosyl-L-methionine (SAMe) had no effect on taurocholate uptake or release, but was able to reverse the competitive inhibition induced by ethinylestradiol. S-Adenosyl-L-homocysteine did not reverse this inhibition, which suggests that the methyl group of SAMe affects its activity. Several possible mechanisms for the action of SAMe were investigated. The methylation of cell membrane phospholipids was eliminated as a possible mechanism. The presence of SAMe greatly increased the catabolism of ethinylestradiol by hepatocytes and reduced its covalent binding to hepatocyte macromolecules. In culture supernatants, both highly polar (conjugated) and non-conjugated metabolites could be detected. Moreover, most of the metabolites were methylated. This suggests that SAMe may revert the effects of ethinylestradiol of taurocholate uptake by increasing its catabolic rate by hepatocytes.