AJP - Renal Physiology, Vol 259, Issue 2 389-F392, Copyright © 1990 by American Physiological Society
Inhibition by (D-Trp12,Tyr34)bPTH(7-34)amide of PTH and PTHrP effects on Pi transport in renal cells
L. Pizurki, R. Rizzoli and J. P. Bonjour
Department of Medicine, University Hospital of Geneva, Switzerland.
We studied the effect of (D-Trp12,Tyr34)bovine parathyroid
hormone-(7-34)amide [(D-Trp12,Tyr34)bPTH(7-34)NH2], a recently described
highly potent antagonist of parathyroid hormone (PTH), on the adenosine
3',5'-cyclic monophosphate (cAMP) and the sodium-dependent phosphate
transport (NaPiT) responses to bPTH-(1-34) or PTH-related protein
[PTHrP(1-34)] in renal epithelial cells. In this system, bPTH and PTHrP
increased cAMP production and inhibited NaPiT in a similar manner.
(D-Trp12,Tyr34)bPTH(7-34)NH2 did not influence either cAMP or NaPiT, but
markedly attenuated the responses to PTH or PTHrP. The effect was
concentration dependent, and a maximal inhibition of PTH or PTHrP effects
was obtained with a 10(3)- to 10(4)-fold greater concentration of the
antagonist. In contrast, the same concentration of the unsubstituted
counterpart, (Tyr34)bPTH(7-34)NH2, which abolished the PTH- or
PTHrP-induced stimulation of cAMP production, did not affect the inhibition
of NaPiT caused by either peptide. Thus (D-Trp12,Tyr34)bPTH(7-34)NH2
inhibited the effects of PTH and PTHrP on both cAMP synthesis and Pi
transport in renal cells. Because of the effects of this analogue on a
transport function affected by these two peptides under physiological and
pathophysiological conditions, it appears to be a promising antagonist.
