Maleic acid administration is known to produce the Fanconi syndrome, although the biochemical mechanism is incompletely understood. In this study the effect of a single injection of maleic acid (50 mg/kg body wt, i.v.) on the rat renal ATPases was examined. Maleic acid rapidly caused bicarbonaturia, natriuresis, and kaliuresis. When nephron segments were microdissected, there was an 81 +/- 2% reduction in proximal convoluted tubule (PCT) Na-K-ATPase activity (P < 0.005) and a 48 +/- 4% reduction in PCT H-ATPase activity (P < 0.01). Enzyme activity (Na-K-ATPase, H-ATPase, H-K-ATPase) in the medullary thick ascending limb of Henle's loop and distal nephron segments was normal. In vitro, maleic acid (1 and 10 mM) inhibited Na-K-ATPase in PCT, but it had no effect on H-ATPase in PCT. Prior phosphate infusion to maleic acid-treated rats attenuated urinary bicarbonate wastage by 50% (P < 0.05); activity of proximal tubule Na-K-ATPase and H-ATPase activities were partially protected as compared to the animals given maleic acid alone (P < 0.05). Renal cortical ATP levels were not altered at the concentration of maleic acid used in this study (that is, 50 mg/kg body wt), but higher doses of maleic acid (that is, 500 and 1000 mg/kg body wt) caused ATP levels to fall. Maleic acid did not affect cortical medullary total phosphate concentration, however, P32 turnover (1 and 24 hr) was altered by prior phosphate infusion. A protective effect of prior phosphate loading on the membrane bound Pi pool (insoluble) was seen while the cytosolic Pi pool (soluble) was not different from control. Thus, maleic acid-induced "Fanconi" syndrome likely results from both direct inhibition of proximal tubule Na-K-ATPase activity and membrane-bound phosphorus depletion. The former mechanism would reduce activity of the sodium-dependent transporters (that is, Na/H antiporter), while the latter would inhibit the electrogenic proton pump (H-ATPase). The combination of reduced proximal tubule Na-H exchange and H-ATPase activities would markedly inhibit bicarbonate reabsorption and result in the metabolic acidosis universally seen in the Fanconi syndrome.

1. A myelin-like membrane fraction was isolated from developing rat brain by a new method. 2. The chemical composition and morphology of the fraction are described. 3. The myelin-like fraction is similar to myelin in characteristic enzyme activity but differs in the absence of basic protein and cerebrosides. No similarity to other subcellular fractions was observed. 4. It is suggested that the myelin-like fraction is a stage in the formation of compact myelin from glial plasma membrane. 5. ;Early' myelin consists of the myelin-like and compact myelin fractions from developing brain.

In previous studies we suggested that urinary tract obstruction and chronic administration of lithium or amiloride were models of "voltage-dependent" distal renal tubular acidosis (DRTA). Subsequently, differences among these three models suggested that the pathogenesis was far more complex than we originally proposed. A recent study showed that H-adenosinetriphosphatase (H-ATPase) activity was decreased in all three experimental models. In the current experiments we examined the effect of 24-h unilateral ureteral obstruction (UUO) and chronic administration of amiloride and lithium on collecting tubule H-K-ATPase, the other renal H-ATPase enzyme. In the obstructed kidney, cortical collecting tubule (CCT) H-K-ATPase activity was enhanced by 73 +/- 10.0%, whereas the enzyme activity in medullary collecting tubule (MCT) was decreased by 67 +/- 5.4%. In the normal contralateral kidney, activities of H-ATPase, H-K-ATPase, and Na-K-ATPase were increased by approximately 30% in both CCT and MCT. Following amiloride (3 mg.kg-1.day-1 x 3 days ip), rats had normal acid-base status, slight hyperkalemia, and markedly elevated plasma aldosterone levels. Both CCT and MCT H-K-ATPase activities in amiloride-treated rats were unchanged. After LiCl (4 meq.kg-1.day-1 x 3 days ip), rats developed mild metabolic acidosis and had normokalemia and normal aldosterone status. CCT H-K-ATPase activity in lithium-treated rats was decreased by 64 +/- 8.8%, whereas the enzyme activity in MCT remained unchanged. Lithium in vitro (30 meq/l) inhibited CCT, but not MCT, H-K-ATPase activity, whereas amiloride had no effect on the enzyme activity. (ABSTRACT TRUNCATED AT 250 WORDS)