2,4-dinitrophenol stimulation of renal ammoniagenesis.
The role of mitochondrial swelling in renal ammoniagenesis was studied by the administration of 10 mg.kg-1 2,4-dinitrophenol, in vivo, to normal and chronically acidotic rats. 2,4-Dinitrophenol increased ammonia excretion in in vivo and in vitro production from glutamine by renal cortical slices and isolated kidneys perfused with 1 mM L-glutamine. Ammonia production per glutamine molecule utilized rose towards 2, consistent with activation of the mitochondrial glutaminase-glutamate dehydrogenase pathway in 2,4-dinitrophenol-treated and acidotic rats. The rank order of 2,4-dinitrophenol stimulation of ammonia formation in vivo and in vitro was normal less than normal + 2,4-dinitrophenol less than acidotic less than acidotic + 2,4-dinitrophenol. 2,4-Dinitrophenol administration appears to enlarge the in situ proximal tubule mitochondrial population and to increase the number undergoing degradation, suggesting that mitochondrial alterations correlate with ammoniagenesis in vivo.
D019297:2,4-Dinitrophenol; D000641:Ammonia / Q000378:metabolism*; D000818:Animals; D004140:Dinitrophenols / Q000494:pharmacology*; D005973:Glutamine / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D011188:Potassium / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000652:urine
D004140:Dinitrophenols; D005973:Glutamine; D000641:Ammonia; D012964:Sodium; D019297:2,4-Dinitrophenol; D011188:Potassium