The Use of Auxiliary Agents to Improve the Mucosal Uptake of Peptides

2004 ◽  
Vol 1 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Andreas Bernkop-Schnurch ◽  
Andreas Clausen ◽  
Davide Guggi
Keyword(s):  
1962 ◽  
Vol 203 (1) ◽  
pp. 73-80 ◽  
Author(s):  
James G. Manis ◽  
David Schachter

Everted gut sacs prepared from the proximal duodenum of the rat, mouse, and golden hamster can transfer iron actively, i.e. against concentration and potential gradients, from the mucosa to the serosa. The active transfer involves two steps: mucosal uptake and net transfer to the serosal surface. Oxidative metabolism is apparently required for each of the steps. Net transfer to the serosal surface is slower, more readily rate-limited, and more sharply localized to the proximal duodenum than is mucosal uptake. Both divalent and trivalent iron are taken up at the mucosal surface, but net transfer to the serosal surface is relatively specific for divalent iron. Calcium inhibits the net serosal transfer of iron at concentrations which do not inhibit the mucosal uptake. Parallel studies with loops of duodenum in living rats indicate that the active, two-step mechanism for iron absorption also functions in vivo, where the steps in the transfer are mucosal uptake followed by transport from the tissue to the blood stream.


Blood ◽  
1993 ◽  
Vol 81 (2) ◽  
pp. 517-521 ◽  
Author(s):  
ME Conrad ◽  
JN Umbreit ◽  
RD Peterson ◽  
EG Moore ◽  
KP Harper

Abstract A mechanism for the absorption of inorganic iron in the small intestine is described in which integrins appear to play an important role in the passage of iron across microvillous membranes. Biochemical isolates from microvillous preparations of duodenum from rats dosed with radioiron showed radioactivity concentrated in integrins. The presence of integrins on mucosal surfaces of duodenal cells was confirmed by immunofluorescent microscopy using anti-integrin monoclonal antibodies. Immunoprecipitation methods were used to show that microvillous radioiron was precipitated with anti-integrin antibodies and that mobilferrin, a 56-Kd cytosol iron-binding protein, coprecipitated with integrins. We postulate from these data that the mucosal uptake of iron from the gut lumen is mediated via an integrin-mobilferrin pathway.


1992 ◽  
Vol 33 (1-3) ◽  
pp. 109-120 ◽  
Author(s):  
Erwin Scharrer ◽  
Esther Senn ◽  
Siegfried Wolffram

Blood ◽  
1980 ◽  
Vol 56 (6) ◽  
pp. 1029-1035 ◽  
Author(s):  
MA Savin ◽  
JD Cook

Using highly sensitive 2-site immunoradiometric assays, we examined the relationship between iron absorption from closed intestinal loops and transferrin and ferritin concentrations in isolated duodenal mucosal cells. As in prior studies, mucosal ferritin correlates inversely with iron absorption and directly with body iron stores as measured by the concentration of nonheme iron in liver. Mucosal transferrin, on the other hand, varies directly with both the total mucosal uptake of radioiron and the proportion of this radioiron transferred from the mucosa to the carcass. The highest correlation with iron absorption was observed with the transferrin-ferritin ratio in isolated mucosal cells. These results suggest that there are two functionally distinct iron- binding compartments in the duodenal mucosa. One is a strong compartment, ferritin, and the other is a transport compartment, transferrin. Control of iron absorption by the intestinal mucosa is closely tied to the balance between these two intracellular iron compartments.


1979 ◽  
Vol 47 (1) ◽  
pp. 87-90 ◽  
Author(s):  
M. Carpenter ◽  
X. J. Musacchia

The effect of 3 wk heat exposure (Ta 34 degrees C) on intestinal weight and intestinal absorption of D-glucose and D-galactose in vitro was examined in the rat. Intestinal dry weight was reduced with heat exposure compared to both ad libitum and pair-fed animals at Ta 22 degrees C. Intestinal tissue water was elevated after pair feeding but not heat exposure; extracellular (inulin) space was similar in the three groups. Mucosal uptake of glucose per gram wet weight in an everted sac preparation was unchanged compared to pair-fed animals, but serosal transfer was increased. Intestinal metabolism of glucose was decreased with heat exposure. Galactose accumulation with 30 min incubation was increased in intestinal rings from both heat-exposed and pair-fed animals. This increase is likely to be related to the reduction in ring size present in the groups with reduced food intake. Vmax and apparent Km for galactose transport were unchanged. Our results indicate that despite a reduction in intestinal weight following heat exposure, the ability of the intestine to transport hexoses per gram remains relatively stable. Alterations of hexose transport appear to be related to altered glucose metabolism and not altered transport capacity. Differences in intestinal weight and glucose utilization between pair-fed and heat-exposed animals suggest that the intestinal response to chronic heat exposure is not solely a function at the amount of food consumed. However, the alteration of more than one variable in pair feeding makes interpretation complex.


1993 ◽  
Vol 17 (3) ◽  
pp. 209-217 ◽  
Author(s):  
G. A. J. Miltenburg ◽  
Th. Wensing ◽  
H. J. Breukink ◽  
J. J. M. Marx

1986 ◽  
pp. 829-839
Author(s):  
Marc Lindheimer ◽  
Jean-Claude Montet ◽  
Jacques Rouvière ◽  
Nicole Kamenka ◽  
Bernard Brun

1963 ◽  
Vol 204 (4) ◽  
pp. 705-709 ◽  
Author(s):  
A. B. Borle ◽  
H. T. Keutmann ◽  
W. F. Neuman

The effect of parathyroid extract (PTE) on phosphate transport was studied by perfusing everted duodenal loops of rats in vitro. It was found that PTE had no effect on the membrane potential or on the pH of the medium. However, PTE increased the influx (transfer from mucosa to serosa) 70%, the uptake by the tissue from the mucosal side 30%, and the lactate transfer into the serosal fluid 30%. Outflux of phosphate (transfer from serosa to mucosa) was as great as the influx but unaffected by PTE. Phosphate uptake from the serosal side was a third of the mucosal uptake and also unaffected by PTE. Metabolic inhibitors, iodoacetate, arsenite, and DNP strongly inhibited phosphate influx and tissue uptake. Lactate formation and transfer were also inhibited by iodoacetate and arsenite but not by DNP. In addition the three inhibitors suppressed completely the PTE effects. It is suggested that phosphate movements across the intestine follow different pathways whose dependence upon metabolism, hormonal action, or electrochemical gradient might be different and independent.


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