Premium
In vivo STUDIES ON AN ANTAGONIST OF PARATHYROID HORMONE [Nle‐8, Nle‐18, Tyr‐34]bPTH‐(3–34)AMIDE
Author(s) -
GRAY DAVID A.,
PARSONS JOHN A.,
POTTS JOHN T.,
ROSENBLATT MICHAEL,
STEVENSON RALPH W.
Publication year - 1982
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1982.tb09215.x
Subject(s) - parathyroid hormone , endocrinology , medicine , in vivo , hypercalcaemia , chemistry , ex vivo , parathyroid hormone receptor , antagonist , adenosine , in vitro , calcium , receptor , biology , biochemistry , hormone receptor , microbiology and biotechnology , cancer , breast cancer
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.