Effect of cAMP analogue infusion on phosphate reabsorption in phosphate-deprived rats

Abstract

The present study was performed to compare the effects of 8-(4-chlorophenylthio)-adenosine 3',5'-cyclic monophosphate (cAMP analogue) and parathyroid hormone (PTH) infusion on segmental phosphate reabsorption in phosphate-deprived rats. Micropunctures of the late proximal and the early distal tubules were performed in acutely thyroparathyroidectomized (TPTX) rats fed either a normal (NPD) or low phosphate diet (LPD), and the phosphaturic response to infusion of PTH and cAMP analogue was evaluated. In NPD rats, PTH (n = 10) and the cAMP analogues (n = 11) markedly increased urinary phosphate excretion, due to inhibition of phosphate reabsorption along the proximal convoluted tubule and pars recta. In phosphate-deprived rats, PTH (n = 10) or the cAMP analogue (n = 11) did not increase urinary phosphate excretion. However, PTH and the cAMP analogue inhibited phosphate reabsorption along the proximal convoluted tubule but not in the pars recta in phosphate-deprived rats. We conclude that cAMP analogue infusion mimics the effect of PTH infusion on phosphate reabsorption along the proximal convoluted and proximal straight tubule in normal and phosphate-deprived rats. The resistance to the phosphaturic effect of PTH and cAMP infusions is a result of a blunted inhibition of phosphate reabsorption by the proximal convoluted tubule and also an increased phosphate reabsorption by the proximal straight tubule.

Npt2 Gene Disruption Confers Resistance to the Inhibitory Action of Parathyroid Hormone on Renal Sodium-Phosphate Cotransport*

“…PTH failed to elicit a phosphaturic response (29,30) or an increase in urinary cAMP excretion (29) in thyroparathyroidectomized rats fed a low Pi diet. PTH failed to elicit a phosphaturic response (29,30) or an increase in urinary cAMP excretion (29) in thyroparathyroidectomized rats fed a low Pi diet.…”

“…To determine whether the failure of renal Pi transport in Npt2 Ϫ/Ϫ mice to respond to PTH could be ascribed to Pi deficiency per se (29,30), we also examined the effect of PTH on the same parameters in Pi-deprived normal mice. Both vehicle-and PTH-treated normal mice responded to the low Pi diet with a marked decrease in the FEI Pi (Fig.…”

Effect of Phosphate Deprivation on Enzymes of the Cyclic Adenosine Monophosphate Metabolism in Rat Proximal Convoluted and Proximal Straight Tubules

“…Since phosphodiesteras es are only one of the primary enzymes by which cAMP is metabolized, this increase in phosphodiesterase activity might be expected to decrease intracellular cAMP levels in the proximal convoluted tubule and also blunt the increase in intracellular cAMP levels in re sponse to PTH. In another study, a selective increase in phosphodiesterase activity in the medullary collecting tubule of the nephrogenic diabetic insipidus mouse has been shown to markedly blunt vasopressin-stimulated cAMP levels in that segment and was also associated with a resistance to vasopressin-induced in creases in water permeability in that segment [9], Acute phosphate deprivation is known to markedly increase phosphate reabsorption and is also associated with a blunted inhibition of phosphate reabsorption to infusions of both PTH and a cAMP analogue along the proximal convoluted tubule [10].…”

Homeostasis of Phosphate Revisited

“…This is indicated by failure of membrane capacity to increase on low P 0 4 diet in diabet ic animals [38, 234] or in normals receiving somatostatin to inhibit insulin release [314], The phosphaturic re sponse to PTH and CT is depressed early [ 198,321] and seems to result mainly from increased reabsorption in the nephron distal to PPC and is relatively insensitive to the hormones while PPC responds near normally [109, 329,330] . Both denervation of the kidney and propranolol mitigate the early response to PTH but not the later [198,331] .…”