In vitro studies on an antagonist of parathyroid hormone [Nle-8, Nle-18, Tyr-34]bPTH-(3-34)amide.

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 volume of 0.3 ml) to 7 day old chicks produced hypercalcaemia 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 less than 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.

journal_name

Br J Pharmacol

authors

Gray DA,Parsons JA,Potts JT Jr,Rosenblatt M,Stevenson RW

doi

10.1111/j.1476-5381.1982.tb09215.x

subject

Has Abstract

pub_date

1982-06-01 00:00:00

pages

259-63

issue

2

eissn

0007-1188

issn

1476-5381

journal_volume

76

pub_type

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