Search

To substantiate our previous hypothesis in explanation of the inhibitory effect of EA, furosemide, and amiloride on mouse intestine, the intracellular potential, Vmc, and transmural potential, Vsm, of the intestinal mucosal epithelium were measured simultaneously with a 0.5-μm diameter microelectrode. It was found when glucose was present in the Ringer bathing solution, an average Vsmof 22.5 ± 0.87 mV was recorded and Vsmwas 2.68 ± 0.09 mV. EA, furosemide, and amiloride at 0.5 mMproduced an hyperpolarization of Vmcand a reduction of Vsm. The Vmcincreased to 34.8 ± 0.68, 31.9 ± 2.6, and 31.2 ± 0.92 mV, respectively. When the bathing fluid contained no glucose, the average Vmcwas 29.5 ± 0.53 mV and the average Vsmwas 1.28 ± 0.10 mV. Addition of EA in the glucose-free bathing media caused no significant change in Vmc, but a decrease in Vsm. However, addition of furosemide or amiloride did cause further hyperpolarizations of Vmc, to 40.7 ± 0.64 and 39.8 ±1.2 mV, respectively. These results support our conclusion that EA mainly acts on the Na-glucose co-transport system and the other two diuretics act on the membrane conductance. The Ar-rhenius plots of the variations of Vsmand Vmcwith temperature provide the calculation of the activation energies for the trans-mural and transmucosal potentials as 19.3 and 14.02 kcal/mole, respectively.

The renal tubular transport of 3-O-methyl-D-glucose (3MG) was studied in dogs and rats. The 3MG was found to be actively secreted by a phlorizin sensitive mechanism in dogs. The nature of the renal handling of 3MG in rats was found to be different from that found in dogs, since, 3MG was reabsorbed by the renal tubules of rats at a rate of about 10% of the 3MG filtration rate. This was interpreted as a result of a reabsorptive process having a larger magnitude than a simultaneously operating secretory process for the same compound. The secretion of 3MG in dogs was found to occur in the proximal tubules and was not inhibited by 2,4-DNP. It was significantly augmented by an intravenous infusion of D-glucose. The results of these experiments were taken as evidence for the existence of a bidirectional sugar transport system in the renal tubules of dogs. This system would be capable of reabsorbing D-glucose and also capable of secreting 3MG and L-glucose.

A simple technic using the mucosal membrane of dogfish gut to study the transport of glucose was presented. It was found that the mucosal membrane can transport glucose from the mucosal to the submucosal fluid against concentration gradients. This transport was greater at 36° than at 26°, and was inhibited by phlorizin, sodium azide, iodoacetic acid and uranyl acetate. Michaelis-Menten analysis of data has shown that inhibition of glucose transport by phlorizin was competitive at 26° and non-competitive at 36°. It is postulated that a carrier system for glucose transport operates at the low temperature, while a more complicated mechanism handles glucose transport at 36°.

Everted intestinal sacs of winter flounders were used in the summer to study the transmucosal movement of glucose and certain aromatic amino acids and derivatives. It was found that glucose was not transported against a concentration gradient. L-tyrosine, D-tyrosine, m-tyrosine, o-tyro-sine, 3-amino-tyrosine, 3,5-dichloro tyrosine and 3,4-dihydroxyphenylalanine were transported from mucosal to serosal side against a concentration gradient. 3,5-dibromo- and 3,5-dinitro-tyrosine were not transported. Among the tryptophan compounds which were studied, only L-tryptophan was transported; D-tryptophan and tryptamine were not transported against a concentration gradient.

With the in vitrokidney slice technique, the in vivosteady state and stopflow technique, we have studied the sites and the interrelationship of tubular secretion and biosynthesis of organic acids and found that both occur in the cortex, in the same proximal segment and probably in the same cells. Addition of transported substance, such as PAH or Diodrast, in the medium does not alter the rate of biosynthesis. Simultaneous administration of aminobenzoic acid does not augment, but exhibits either no effect or a slight decrease of tubular transport maximum of the aminohippurate. However, administration of Diodrast would markedly depress the urinary excretion of aminohippurate either by administration or by biosynthesis. Our results indicate that the second step of the transport process, from cell to lumen, is carrier-mediated, and that this carrier can be saturated at a Tm level.