AJP - Endocrinology and Metabolism, Vol 262, Issue 4 E483-E487, Copyright © 1992 by American Physiological Society
Dissociation of phosphaturia and 25(OH)D-1 alpha-hydroxylase trophism using a novel analogue of parathyroid hormone
T. O. Carpenter, M. D. McPhee, R. Bort, M. A. Mitnick and D. L. Carnes
Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut 06510.
Certain parathyroid hormone (PTH) analogues have been shown to selectively
impair some but not all physiological actions of PTH. In this study,
transaminated rat (r) PTH [TA-rPTH-(1-34)], a PTH analogue that differs
from the rPTH-(1-34) fragment in that the NH2-terminal alanine is converted
to pyruvate, was infused into mice to determine its properties in vivo and
specifically to determine whether stimulation of 25-hydroxyvitamin D-1
alpha-hydroxylase (1 alpha-hydroxylase) activity was more dependent on
concomitant renal handling of phosphate or on generation of adenosine
3',5'-cyclic monophosphate (cAMP). High-performance liquid
chromatography-purified TA-rPTH-(1-34) was infused into C57BL mice at 10 or
30 pmol/h for 24 h. At 30 pmol/h, TA-rPTH-(1-34) was comparable with
rPTH-(1-34) in its hypophosphatemic and phosphaturic effects but was less
potent than rPTH-(1-34) in raising serum calcium. TA-rPTH-(1-34) was
markedly less effective in stimulating renal 1 alpha-hydroxylase than
rPTH-(1-34). Stimulation of urinary cAMP excretion occurred after infusion
with TA-rPTH-(1-34), but this effect was significantly less than that seen
with rPTH-(1-34). These findings indicate that PTH-induced hypophosphatemia
and phosphaturia can be uncoupled from PTH stimulation of 1
alpha-hydroxylase. Furthermore, cAMP-related signal transduction appears to
be more significant in regulation of 1 alpha-hydroxylase than mechanisms
that mediate PTH-sensitive phosphate transport, independent of cAMP.
