Aspirin, protein transacetylation and inhibition of prostaglandin synthetase in the kidney.
1 The effect of aspirin on the kidney has been investigated in mice and rabbits. [Acetyl-(14)C]-aspirin was administered intraperitoneally in doses ranging from subtherapeutic to toxic. The degree of acetylation of protein was determined by the radioactivity remaining on protein precipitates of renal cortex and medulla after sequential washing designed to remove non-covalently bound material. Controls were established, by the use of [carboxyl-(14)C]-aspirin.2 The acetyl-(14)C residue was bound to renal proteins in a linear manner in increasing amounts with increasing dosage up to 100 mg/kg. The [carboxyl-(14)C]-aspirin was not bound and thus the salicylate portion of the molecule was not bound covalently to the renal protein. The time course of the acetylation was rapid, consistent with the rate of aspirin absorption. The disappearance of acetylated protein was slow, with a T(1/2) of 112.5 h in the renal cortex, and 129.5 h in the renal medulla.3 Differential centrifugation, Sephadex chromatography and gel electrophoresis were carried out on tissue homogenates to determine the site of acetylation. The acetylation was greatest in the microsomal fraction, although all protein fractions showed some degree of acetylation.4 The prostaglandin synthetase activity of a particulate preparation from rabbit kidney was determined by a spectrophotometric assay of malondialdehyde formation. Aspirin (10 mg/kg, i.v.) significantly inhibited prostaglandin synthetase in the renal cortex and medulla.5 Aspirin and renal proteins undergo a transacetylation reaction resulting in stable acetylated protein, with acetylation being greatest in the microsomal fraction. Aspirin has been shown to inhibit prostaglandin synthetase and this could lead to functional impairment of the tissue.
D000107:Acetylation; D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors; D007668:Kidney / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011506:Proteins / Q000378:metabolism*; D011817:Rabbits
D016861:Cyclooxygenase Inhibitors; D011506:Proteins; D008315:Malondialdehyde; D001241:Aspirin