Urinary inhibitor of the ammoniagenic response to acute acidosis is a prostaglandin.
Both acute respiratory acidosis and acute metabolic acidosis stimulate NH3 production by the isolated perfused rat kidney. This stimulatory effect is abolished if the urine is drained back into the recirculating perfusate rather than collected. To determine whether the urinary inhibitor is a cyclooxygenase product, studies were carried out using prostaglandin synthetase inhibitors. Kidneys perfused with 0.5 mmol/L glutamine and urine reinfusion were subjected to acute respiratory acidosis (30% CO2, pH 6.8). With either indomethacin (20 mumol/L) or meclofenamate (20 mumol/L) in the perfusate, NH3 production increased significantly in response to acute respiratory acidosis despite urine reinfusion. The increment in NH3 production was comparable to that in studies with urine collection, indicating that a cyclooxygenase product can account completely for the urinary inhibitor. To further characterize the urinary prostaglandin inhibitor, studies were performed with both the isolated perfused kidney and renal cortical tubules. Prostaglandin E2 (PGE2) did not exhibit an inhibitory effect on NH3 production with either experimental model. Prostaglandin F2 alpha at low doses inhibited NH3 production in response to acute acidosis by the isolated kidney, but an effect was not apparent with higher concentrations. PGF2 alpha inhibited the stimulatory effect of a low pH (7.1) on NH3 production by isolated tubules, and had no effect on ammoniagenesis at pH 7.4. Thus a prostaglandin, which is not PGE2 and may be PGF2 alpha, appears to be the previously unidentified urinary inhibitor of the ammoniagenic response to acute acidosis found with the isolated perfused kidney.
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D000142:Acidosis, Respiratory / Q000652:urine*; D000641:Ammonia / Q000096:biosynthesis*; D000818:Animals; D015237:Dinoprost; D015232:Dinoprostone; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007684:Kidney Tubules / Q000378:metabolism; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D010477:Perfusion; D011453:Prostaglandins / Q000502:physiology / Q000652:urine*; D011458:Prostaglandins E / Q000494:pharmacology; D011460:Prostaglandins F / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D011453:Prostaglandins; D011458:Prostaglandins E; D011460:Prostaglandins F; D008469:Meclofenamic Acid; D000641:Ammonia; D015237:Dinoprost; D015232:Dinoprostone; D007213:Indomethacin