Renal refractoriness to PTH in experimental Fanconi syndrome: evidence for intact adenylate cyclase activation.
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 (mean +/- SE) to 16.8 +/- 3.5 pmoles cAMP/mg prot/min (P less than 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 less than 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 less than 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 less than 0.001). For the difference in the increment between the control and FS group, P less than 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 less than 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.(ABSTRACT TRUNCATED AT 250 WORDS)
D000255:Adenosine Triphosphate / Q000032:analysis; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D000242:Cyclic AMP / Q000032:analysis; D004789:Enzyme Activation; D005198:Fanconi Syndrome / Q000139:chemically induced / Q000201:enzymology* / Q000378:metabolism; D007672:Kidney Cortex / Q000032:analysis / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D008298:Maleates; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010710:Phosphates / Q000652:urine; D051381:Rats
D008298:Maleates; D010281:Parathyroid Hormone; D010710:Phosphates; D000255:Adenosine Triphosphate; C030272:maleic acid; D000242:Cyclic AMP; D000262:Adenylyl Cyclases