The ionophore A23187 at a concentration of 10(-7) to 10(-5) M stimulated active transport of Cl across the isolated frog cornea. The ionophore had no effect in a Cl-free medium. Both unidirectional Cl fluxes were increased by A23187. The electrical resistance was decreased, and this can be totally accounted for by the increment in passive Cl fluxes. The effect of A23187 on Cl transport and permeability mimicked the effects of cyclic AMP, isoproterenol, and epinephrine. A23187 had no effect when the corneas were fully stimulated by epinephrine or isoproterenol. A23187 produced normal stimulation of the SCC in corneas pretreated with alpha- and beta-adrenergic blockers. The stimulation of the SCC by A23187 was dependent on the presence of Ca in the Ringer solution. Excess Ca (10 mM) resulted in a reduced response. Increasing the Mg concentration in the medium reduced the stimulation of the SCC with Ca concentrations of 0.1-5 mM, but prevented the relative inhibition of 10 mM Ca. Intracellular Ca concentration seemed to regulate Cl permeability of the cornea.
The administration of alkaline agents to a 16-year-old girl with severe renal tubular acidosis and osteomalacia caused an almost immediate rise of the urinary excretion of total hydroxyproline. The increment of the dyalizable fraction predominated over the nondyalizable component. Gradually serum phosphate and serum alkaline phosphatase increased whereas urinary calcium and magnesium and phosphate clearance declined. Serum PTH remained elevated throughout. We suggest that the correction of the metabolic acidosis might increase the transport of phosphate and calcium across the functional bone membrane leading to a rapid deposition of lime salts in the uncalcified matrix with a concomitant increase in bone collagen turnover.
The effect of actinomycin D, cycloheximide and glucocorticoids on the intestinal absorption of phosphate was studied. The effective intestinal absorption of 32P and 47Ca was determined simultaneously in intact rats in vivo using a whole body counter. Both, actinomycin D and cycloheximide caused a significant diminution of the intestinal absorption of phosphate whereas calcium absorption was not altered. Experiments with the in situ ligated loop technique were performed to eliminate the possibility that the action of the protein synthesis inhibitors could be due to an altered intestinal motility effect. Phosphate absorption was also significantly diminished under this condition. On the other hand, the administration of glucocorticoids produced a significant inhibition of phosphate and calcium absorption in the rat in vivo. The reported results indicate that proteins and/or enzymes with a rapid turn-over are involved in the mechanism of phosphate intestinal absorption, and confirm previous observations that phosphate and calcium are transported across the intestine by different mechanisms.
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