Add time:07/25/2019 Source:sciencedirect.com
Effects of demethylchlortetracycline (cas 106276-91-9) on cellular action of antidiuretic hormone in vitro. Demethylchlortetracycline (DMC) can induce a syndrome of nephrogenic diabetes insipidus in man without affecting other renal functions. Because this pathologic change might be due to interference with the cellular action of antidiuretic hormone (ADH) on the distal nephron, we studied, in vitro, the effect of DMC on some enzymes of the ADH-dependent cyclic AMP (cAMP) system prepared from human renal medulla. Increasing concentrations of DMC produced increasing inhibition of adenylate cyclase basal activity and of the activity stimulated by ADH or by sodium fluoride; at a DMC concentration of 500 µg/ml the inhibition was about 50%. The inhibition appears to be noncompetitive. The same doses of DMC produced only slight inhibition of cAMP diesterase. cAMP-dependent protein kinase contained in cytosol of renal medulla also was inhibited by DMC. Therefore, DMC has the potential to inhibit cAMP formation and the accumulation of cAMP in the renal medulla in response to ADH and also to inhibit cAMP-dependent phosphorylation of proteins in the renal medulla. It is suggested that differential inhibition of these enzymes might be the basis of the unresponsiveness to ADH induced by this drug in vivo. Tetracycline and chlortetracycline had the same effects as DMC in vitro. Additional factors would probably determine why the effect is apparent in vivo only after administration of DMC.
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