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Biomedical subjects

F V Sepúlveda

Publications and source records attributed to F V Sepúlveda.

97 records · Page 6Linked to original sources

Differential effects of harmaline and ouabain on intestinal sodium, phenylalanine and beta-methyl-glucoside transport.

Harmaline inhibits both the Na+ -K+ -ATPase activity and the uptake of L-phenylalanine in guinea-pig intestinal mucosa. The latter effect is not a direct consequence of the former, since higher concentrations are needed to inhibit the enzyme than the influx into the mucosa; Furthermore the uptake is still sensitive to harmaline when the Na+ -K+ -ATPase has been fully inhibited by ouabain. Harmaline can inhibit L-phenylalanine influx at a concentration at which it does not affect intracellular ion concentrations. Ouabain, however, inhibits the uptake of L-phenylalanine only after a 30 min preincubation period, when the intracellular sodium concentration reached the extracellular level. Harmaline also interferes with the influx of beta-methyl-D-glucoside in the mucosa of the dog colon. Addition of harmaline at the mucosal face of the tissue suppresses all net transport of sodium and chloride ions and L-phenylalanine across the mucosa. Thus the same mode of action appears to apply in both the guinea-pig ileum and the dog colon.

Adenosine Triphosphatases↗

The functional response of the dog ileum to one hour's ischaemia.

1. The function and structure of dog ileal mucosa was examined immediately after arterial ischaemia for 1 h and 1, 3 or 7 days after the trauma. 2. Immediately after the ischaemia, there was a net movement of water and ions into a luminal perfusate in vivo. One day later, there was no net movement of water and electrolytes but net absorption returned on the third day. 3. Active transport of phenylalanine or beta-methylglucoside by mucosal strips in vitro was abolished immediately after the trauma but was largely restored 1 day later. There was a close correlation between glucose absorption in vivo and beta-methylglucoside uptake in vitro. 4. Morphological study revealed pronounced desquamation of enterocytes immediately after the trauma. The regenerating mucosa had shorter villi and crypts, and lower enzyme activities assessed histochemically 1 day later. Most parameters had returned to normal by the third post-operative day.

Acid Phosphatase↗

Active amino-acid and sugar uptake by gall bladder epithelium in dog, guinea-pig and man.

Slices of dog gall bladder are capable of accumulating amino-acids and sugars against considerable concentration gradients across the luminal membrane of the cell. The epithelium of the common bile duct also absorbs these substrates. The transport systems are sodium-dependent, saturable and inhibited by ouabain and metabolic poisons. The specificity of the mechanisms is more reminiscent of kidney than of intestinal transport. Glycine is preferentially transported across dog gall bladder from the mucosa to the serosa, but the net flux is small. It is concluded that the contraluminal membrane of the epithelial cell might be relatively impermeable to the amino-acid. concentrative uptake also occurs in guinea-pig gall bladder; however it appears to be practically non-existent in rabbit tissue. Human gall bladders, obtained at random from the operating room, also displayed active accumulation. The gall bladder epithelium is remarkably resistant to anoxia. Furthermore, following obstruction of the common bile duct for 2 weeks in dogs, the gall bladder is still able to concentrate amino-acids and sugars, but the extent of the uptake is significantly reduced.

Amino Acids↗

New characteristics of harmaline inhibition of intestinal transport systems.

Harmaline strongly inhibits the uptake of phenylalanine by slices of guinea-pig intestine in vitro. The lowest concentration having a significant effect is 0.1 mM. The drug also inhibits the unidirectional flux of phenylalanine from the mucosal to serosal face of the tissue provided it is added to the solution bathing the mucosal surface. The unidirectional flux of sodium from the mucosa to the serosa was similarly reduced. Ion and water absorption in the perfused dog intestine in vivo is also diminished in the presence of harmaline. These results support the hypothesis, previously proposed in view of the rapid onset of harmaline inhibition of sodium-dependent uptake mechanisms in a variety of tissues, that harmaline interacts with the sodium-site of non-electrolyte carrier complexes. The effect of harmaline on phenylalanine uptake by the intesting is duplicated by other psychotropic indole analogues. The actions of harmine and harnalol are similar to that of harmaline, despite great differences in the liposolubility of the different compounds. N:N-dimethyl-tryptamine is equally inhibitory, but serotonin is inactive. Mescaline and lysergic acid diethylamide also inhibit phenylalanine transport, but to a much lesser extent than harmaline.

Alkaloids↗