Abstract
Previous studies demonstrated renal refractoriness to parathyroid hormone (PTH) in maleate-induced Fanconi syndrome (FS) in rats.
In membrane fraction of renal cortex of parathyroidectomized (PTX) rats with FS, PTH increased adenylate cyclase (AC) activity from a basal value of 7.4±0.6 (x±SE) to 16.8±3.5 pmoles cAMP/mg prot/min (P<0.01), similar stimulation by PTH was observed in control incubation with normal kidneys. In membrane fraction of renal cortex of PTX rats incubated with maleate, PTH increased AC from 5.7±0.42 to 10.7±1.08 (P<0.01) similar to control incubation without maleate.
In cortical slices from PTX rates with FS incubated in vitro, PTH increased cAMP content only from 4.0±0.21 to 5.27±0.27 pmole cAMP/mg prot (P<0.005), while in slices from the control group the increment by PTH was from 3.9±0.43 to 10.7±0.93 pmoles cAMP/mg prot (P<0.001). For the difference in the increment between the control and FS group,P<0.001.
In cortical tissue of PTX rats with FS, PTH injection failed to increase cAMP content: basal value 7.4±0.8 and with PTH 9.2±0.8 pmole cAMP/mg prot (P NS), as compared with controls: basal value 9.5±0.5 and with PTH 23.8±1.6 (P<0.001). ATP content of cortical slices fell from a control value of 2.3±0.18 in PTX rats to 1.0±0.14 nmol/mg prot in PTX rats with FS.
These results show, (1) normal response to PTH stimulation of cortical AC from rats with FS, and (2) failure of PTH to enhance formation of cAMP in renal cortical tissue from rats with FS. These findings are consistent with an intact PTH receptor/AC system in maleate induced FS, but inability to increase cAMP production probably because of comprized cellular metabolism causing reduced ATP content.
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Wald, H., Popovtzer, M.M. Renal refractoriness to PTH in experimental Fanconi syndrome: Evidence for intact adenylate cyclase activation. Pflugers Arch. 402, 116–119 (1984). https://doi.org/10.1007/BF00584840
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DOI: https://doi.org/10.1007/BF00584840