1. This study was performed to test the hypothesis that glycosaminoglycans may play an important role in the observed abnormalities in oxalate flux seen in patients with calcium oxalate nephrolithiasis. 2. Oxalate flux rate, erythrocyte membrane glycosaminoglycan content, membrane protein phosphorylation and effect of heparan sulphate on erythrocyte oxalate flux in vitro were studied in control subjects and patients with calcium oxalate nephrolithiasis. 3. In comparison with control subjects, renal stone-formers showed a significantly higher oxalate self-exchange, a lower erythrocyte membrane glycosaminoglycan content and a higher membrane phosphorylation rate. In stone-formers, erythrocyte glycosaminoglycan content correlated inversely with both oxalate flux rate and protein phosphorylation. In vitro , heparan sulphate promoted a significant fall in the rate of oxalate self-exchange. 4. These findings support the hypothesis that a lower erythrocyte membrane content of glycosaminoglycans enhances membrane protein phosphorylation, leading to an increased rate of transmembrane oxalate flux.

1. Since prostaglandin E 2 could play a role in idiopathic hypercalciuria, and considering the well-established hypocalciuric action of hydrochlorothiazide, we have evaluated the effect of 15 days' treatment with hydrochlorothiazide in 10 hypercalciuric male stone-formers on urinary Ca 2+ and prostaglandin E 2 , as well as on plasma bicyclo-prostaglandin E 2 , 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and parathyroid hormone. 2. In addition to lowering urinary Ca 2+ ( P <0.001), hydrochlorothiazide also promoted a significant fall in urinary prostaglandin E 2 ( P <0.001), plasma bicyclo-prostaglandin E 2 ( P <0.001) and 1,25-dihydroxyvitamin D ( P <0.01), and an increase in plasma parathyroid hormone ( P <0.025), whereas plasma 25-hydroxyvitamin D was unchanged. 3. A positive correlation between urinary Ca 2+ and prostaglandin E 2 was present before ( P <0.00005), but not after, hydrochlorothiazide. Plasma bicyclo-prostaglandin E 2 and plasma 1,25-dihydroxyvitamin D were positively correlated both before ( P <0.005) and after ( P <0.005) hydrochlorothiazide, as was also the percentage change in each induced by the drug ( P <0.05). Furthermore, the changes in plasma 25-hydroxyvitamin D and plasma 1,25-dihydroxyvitamin D after hydrochlorothiazide were negatively correlated ( P <0.05). 4. It is suggested that a block of prostaglandin E 2 synthesis plays a role in the effect of hydrochlorothiazide on Ca 2+ metabolism, most probably through an inhibition of 1α-hydroxylase activity.

1. Cytosolic free calcium concentrations ([a 2+ ] i ) were measured in resting and chemotactic peptide-activated neutrophils from eight patients with Bartter's syndrome and compared with levels determined in neutrophils isolated from healthy controls. 2. [Ca 2+ ] i was measured with the intracellular trappable fluorescent indicator Quin2. The synthetic tripeptide formylmethionyl-leucyl-phenylalanine (fMet-Leu-Phe) was used as a stimulant. 3. No difference was found in resting [Ca 2+ ] i between neutrophils from normal controls and those from patients with Bartter's syndrome. 4. On the contrary increases in [Ca 2+ ] i stimulated by fMet-Leu-Phe concentrations higher than 10 −8 mol/l were significantly less in neutrophils from patients with Bartter's syndrome. 5. It is suggested that neutrophils from patients affected by Bartter's syndrome exhibit an intrinsic anomaly in the mechanism responsible for intracellular Ca 2+ mobilization.