Comparison of the effects of parathyroid hormone (PTH) and recombinant PTH-related protein on bicarbonate excretion by the isolated perfused rat kidney

Abstract

The isolated perfused rat kidney was used to study the effects of amino-terminal fragments of human parathyroid hormone, hPTH(1-34), bovine parathyroid hormone, bPTH(1-84) and of PTH-related proteins, PTHrP(1-34), PTHrP(1-84), PTHrP(1-108) and PTHrP(1-141) on urinary bicarbonate excretion. PTHrP(1-34) (7 nmol/l), bPTH(1-84) (5.5 nmol/l) and hPTH(1-34) (7 nmol/l) had similar effects in increasing bicarbonate excretion with respect to the control. At lower concentrations (0.7 nmol/l) all PTHrP components, but not hPTH(1-34) or bPTH(1-84) increased bicarbonate excretion significantly. Infusions of PTHrP(1-108) and PTHrP(1-141) at 0.7 nmol/l, while associated with a rise in urinary bicarbonate concentration and excretion during the early stages of perfusion, produced a sharp decline in bicarbonate concentration and excretion in the latter part of perfusion. The different peptides produced no significant differences in glomerular filtration rate, fractional excretion of sodium or urine volume. The absence of substantial differences between the effects of hPTH(1-34) and PTHrP(1-34) are as noted in previous studies. The differences between PTHrP(1-108)/PTHrP(1-141) and PTHrP(1-34) demonstrated here are consistent with (1) the clinical manifestations of acidosis in hyperparathyroidism and alkalosis in humoral hypercalcaemia of malignancy, and (2) an independent action of a component of PTHrP beyond amino acids 1-34.