Extraction of Parathyroid Hormone and Release of Adenosine 3′,5′-Monophosphate by Isolated Perfused Bones Obtained from Dogs with Acute Uremia*

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Abstract
To study the direct effect of PTH on bone in acute uremia, we examined the effects of bilateral nephrectomy (BNX) and a combination of BNX and thyroparathyroidectectomy (TPTX) on the arteriovenous difference of PTH-(1–34) and the release of cAMP by the isolated perfused tibia of the dog. Normal dogs were subjected to BNX or TPTX-BNX, and 42 h later, the tibiae were removed for perfusion. The immunoreactive PTH levels in plasma were significantly elevated in the BNX group. The mean extraction of PTH-(1–34) by bone was 46.7 ± 6.3% in the control group and not significantly different in any of the experimental groups. The release of cAMP increased significantly in all groups (P < 0.005 to P < 0.001) after the administration of PTH-(1–34). The cumulative release of cAMP per 30 min was significantly diminished (P < 0.001), compared to controls, in the BNX groups, but was normal in the TPTX-BNX group. In conclusion, isolated perfused bones from acutely bilaterally nephrectomy dogs release less cAMP in response to PTH-(1‐34) administration than bones from normal control dogs. This decrease in cAMP release was totally abolished by simultaneous BNX and TPTX. This suggests that an abnormal response of the adenylate cyclase system of bone to PTH may exist in acute uremia, probably secondary to the high plasma levels of PTH found in this condition.