Lithium administration and phosphate excretion

Abstract

The phosphaturic effect of parathyroid hormone (PTH), cyclic adenosine monophosphate (cAMP), acetazolamide (Az), and HCO3 loading was studied in normal, thyroparathyroidectomized (TPTX), and Li-treated dogs. PTH administration to normal animals markedly increased fractional excretion (F) of PO4 but had a blunted effect on FPO4 in the Li-treated animals. Cyclic AMP likewise markedly increased FPO4 in the normal animals but had a markedly blunted effect in the Li-treated animals. Az led to a significant increase in FNa, FHCO3, and FPO4 in the normal animals. In the Li-treated dogs, Az induced a significant natriuresis and bicarbonaturia but failed to increase phosphaturia. HCO3 loading in normal dogs caused a significant phosphaturia while having little effect on FPO4 in Li-treated dogs. HCO3 loading to TPTX dogs was associated with a lower FPO4 as compared to normal HCO3-loaded animals. These data suggest that Li administration not only blocks the adenyl cyclase-cAMP system in the renal cortex, but it may also interfere with a step distal to the formation of cAMP, since the phosphaturic effect of both PTH and cAMP was markedly diminished in Li-treated animals.

Lithium effects on calcium, magnesium and phosphate in man: effects on balance, bone mineral content, faecal and urinary excretion

“…Lithium treatment decreased the urinary calcium and phosphate excretion, effects which have also been observed by others ( Arruda et al (1976), Bjlrum et al (1975), Crammer (1975), Miller et al (1978), Nielsen et al (1977, Perey et al (1977), Sfeele (1976)), and resulted in a positive balance of both elements (Tables 2 and 3).…”

Lithium interactions with Na+-coupled inorganic phosphate cotransporters: insights into the mechanism of sequential cation binding

“…8B) and contribute to net charge movement. 2 However, we found that Q max for 100Li superfusion was Ϸ70% of that obtained for 100Na. One mechanistic interpretation of this finding is that for superfusion in 100Li, Li ϩ ions move across a smaller fraction of the transmembrane electric field to reach their binding site compared with Na ϩ ions.…”

“…10). This behavior of V 0.5 vs. log 10 [X] (X ϭ Na or Li) can be 2 The 100Li result contrasts with our previous study (30) on the flNaPi-IIb mutant S448C in which no change was reported and might be attributable to the effect of the cysteine mutation on cation interactions or to more precise estimation of charge movement possible from WT expressing oocytes in the present study that were selected with ԽIP i Խ Ն 400 nA (1 mM Pi). Fig.…”

“…In one of the few reports (25) that has addressed the effects of Li ϩ on renal P i handling, it appears that P i clearance and tubular reabsorption are normal in humans undergoing chronic Li ϩ therapy, unlike the case for dicarboxylates. Moreover, in two animal studies, the effect of high doses of Li ϩ on P i handling would appear to result from an indirect action on PTH regulation of NaPi-II abundance in the brush border membrane, as opposed to an interaction with cation binding sites within the transport protein (2,32).…”

Acute Lithium Administration Impairs the Action of Parathyroid Hormone on Rat Renal Calcium, Magnesium and Phosphate Transport*

“…Chronic Li' treatment also inhibits proximal PTH-mediated phosphate transport, possibly by blocking the adenyl cyclase-cAMP system. 34 In conclusion, the acute administration of Li' to the anaesthetized rat appears to inhibit the action of both endogenous and administered PTH on Ca2', Mg" and phosphate transport. This effect appears to be related to the plasma Li' concentration and, while it may occur in more than one nephron site, the thick ascending limb is the most likely site of action.…”