Effects of tinoridine on lipid peroxidation and renin release in the rat renin granule fraction.
This study was carried out to investigate the effect of tinoridine (2-amino-3-ethoxycarbonyl-6-benzyl-4,5,6,7-tetrahydrothieno[2,3-c] pyridine), a non-steroidal anti-inflammatory drug, on the lipid peroxidation and renin release in the renin granule fraction. The renin granule fraction was prepared from the kidney cortex homogenate by a discontinuous sucrose density gradient centrifugation. Incubation of this fraction at 37 degrees C resulted in an increase in lipid peroxide formation, accompanied by increased release of renin from the granules. When the renin granule fraction was incubated with 50 microM tinoridine at 37 degrees C, lipid peroxide formation in this fraction was completely inhibited. Simultaneously, the rate of renin release from the granules was significantly suppressed. Tinoridine, at concentrations from 5 microM up to 100 microM, produced a concentration-dependent inhibition on the simultaneous increases in lipid peroxide formation and renin release induced by 50 microM ascorbic acid in the renin granule fraction. On the other hand, indomethacin, hydrocortisone and prednisolone, which had no ability to inhibit the lipid peroxidation in the renin granule fraction, did not influence the release of renin from the granules. These results suggest that tinoridine suppresses renin release by inhibiting the oxidative disintegration of membranes of renin granules.
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D003594:Cytoplasmic Granules / Q000378:metabolism; D006854:Hydrocortisone / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008054:Lipid Peroxides / Q000378:metabolism*; D008297:Male; D011239:Prednisolone / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000378:metabolism*; D058924:Thienopyridines; D013997:Time Factors
D008054:Lipid Peroxides; D011725:Pyridines; D058924:Thienopyridines; D011239:Prednisolone; C100290:tinoridine; D012083:Renin; D001205:Ascorbic Acid; D006854:Hydrocortisone; D007213:Indomethacin