Antioxidant inhibition of prostaglandin production by rat renal medulla. |
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Authors: | T V Zenser B B Davis |
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Institution: | 1. Geriatric Center, Veterans Administration Hospital, St. Louis, Mo. USA;2. the Department of Medicine, St. Louis University, St. Louis, Mo. USA;3. the Department of Biochemistry, St. Louis University, St. Louis, Mo. USA |
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Abstract: | Antioxidant effects upon renal production of both prostaglandins and cAMP were investigated using slices of rat inner medulla. Synthetic antioxidants were more potent inhibitors of prostaglandin production than were naturally occurring antioxidants. Synthetic compounds 2,7-naphthalenediol, and Santoquin® (Ethoxyquin) caused a 60% inhibition of prostaglandin E2(PGE2) synthesis at a concentration of 0.01 mM. Ascorbic acid caused only a 30% inhibition at a concentration of 10 mM. Antioxidant inhibition of prostaglandin production was also observed following arachidonic acid addition. Antioxidants that reduced PGE2 synthesis also reduced PGF2α synthesis. Test agents found to reduce prostaglandin synthesis also lowered cAMP content. 2,7-Naphthalenediol elicited a dose-dependent decrease in both prostaglandin synthesis and cAMP content. While PGE1 did not increase cAMP in control slices, the low cAMP level produced by Santoquin was increased to control values by PGE1. Furthermore, Santoquin and 2,7-naphthalenediol did not alter arginine vasopressin-stimulated cAMP content. By contrast, inhibition of the arginine vasopressin stimulation by butylated hydroxyanisole suggested additional effects by this agent. These results are consistent with the hypothesis that endogenously produced PGE2 can exert a hormonelike action in the inner medulla by increasing cAMP content. Advantages of the inner medullary slice system compared to homogenates for investigation of the actions of antioxidants or other agents thought to alter prostaglandin synthesis are discussed. |
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Keywords: | Reprint requests should be addressed to Terry V Zenser Ph D Geriatric Center VA Hospital St Louis Mo 63125 |
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