Aminoglycoside toxicity: pH dependent inhibition of ADH response

The effect of aminoglycoside antibiotics on the response of the isolated toad urinary bladder to antidiuretic hormone (ADH) was investigated. Gentamicin and neomycin both acidify the serosal bathing solution and cause a dose-dependent inhibition of the hydroosmotic response to ADH, while streptomycin has minimal effect on media pH and causes no inhibition of the response to ADH. Detailed studies employing gentamicin indicate that acidification stimulates production of PGE2, a known inhibitor of the hydroosmotic response of the toad bladder to ADH. When media pH is rigidly controlled or PGE2 production is inhibited by indomethacin, the inhibitory effect of gentamicin on the response to ADH is ameliorated. These studies suggest that the defect in renal concentrating ability seen as part of aminoglycoside nephrotoxicity could be due, in part, to an acidification-induced, prostaglandin-mediated resistance to the action of ADH.