Article date: June 1982
By: DAVID A. GRAY, JOHN A. PARSONS, JOHN T. POTTS, MICHAEL ROSENBLATT, RALPH W. STEVENSON in Volume 76, Issue 2, pages 259-263
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.
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.
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).
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.
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.
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.
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.
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).
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.
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.
DOI: 10.1111/j.1476-5381.1982.tb09215.x
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