In vivo STUDIES ON AN ANTAGONIST OF PARATHYROID HORMONE [Nle‐8, Nle‐18, Tyr‐34]bPTH‐(3–34)AMIDE

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Abstract
1 The actions of parathyroid hormone (PTH) are antagonized in vitro by the peptide [Nle-8, Nle-18, Tyr-34]-bPTH-(3–34)amide, an analogue of PTH. In this paper, the actions of the inhibitory peptide were investigated in vivo. 2 Native parathyroid hormone (bPTH-(1–84)), administered i.v. (0.17–1.51 nmol in a volume of 0.3 ml) to 7 day old chicks produced hypercalcemia but administration of the analogue in doses up to 173 nmol was ineffective in this respect. 3 The analogue failed to antagonize the hypercalcaemia produced by bPTH-(1–34) when injected, in 10 fold molar excess, 2 min before or simultaneously with bPTH-(1–34). 4 Normocalcaemia was restored in parathyroidectomized rats by intravenous infusion of bPTH-(1–84) at 32 pmol kg−1 h−1. Addition of the analogue to the infusion fluid in a 200 fold molar excess did not affect the concentrations of calcium and phosphate in the plasma, cyclic adenosine 3′,5′-monophosphate (cyclic AMP) in the urine or phosphate clearance but produced a significant (P< 0.05) rise in urinary calcium clearance. 5 The results suggest that the peptide [Nle-8, Nle-18, Tyr-34]-bPTH-(3–34)amide does not antagonize the actions of PTH in vivo and demonstrate an important dichotomy between in vitro and in vivo biological properties of the PTH analogue.