• The Korean Journal of Physiology and Pharmacology
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• 제2권4호
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• pp.521-527
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• 1998

An important property of the intestine is the ability to secrete fluid. The intestinal secretion is regulated by a number of substances including vasoactive intestinal peptide (VIP), ATP and different inflammatory mediators. One of the most important secretagogues is adenosine during inflammation. However, the controversy concerning the underlying mechanism of adenosine-stimulated $Cl^-$ secretion in intestinal epithelial cells still continues. To investigate the effect of adenosine on $Cl^-$ secretion and its underlying mechanism in the rabbit colon mucosa, we measured short circuit current ($I_{SC}$) under automatic voltage clamp with DVC-1000 in a modified Ussing chamber. Adenosine, when added to the basolateral side of the muocsa, increased $I_{SC}$ in a dose-dependent manner. The adenosine-stimulated $I_{SC}$ response was abolished when $Cl^-$ in the bath solution was replaced completely with gluconate. In addition, the $I_{SC}$ response was inhibited by a basolateral Na-K-Cl cotransporter blocker, bumetanide, and by apical $Cl^-$ channel blockers, dephenylamine-2-carboxylate (DPC), 5-nitro-2-(3-phenyl-propylamino)-benzoate (NPPB), glibenclamide. Amiloride, an epithelial $Na^+$ channel blocker, and 4,4-diisothiocyanato-stilbene-2,2-disulphonate (DIDS), a $Ca^{2+}-activated$ $Cl^-$ channel blocker, had no effect. In the mucosa pre-stimulated with forskolin, adenosine did not show any additive effect, whereas carbachol resulted in a synergistic potentiation of the $I_{SC}$ response. The adenosine response was inhibited by 10 ${\mu}M$ H-89, an inhibitor of protein kinase A. These results suggest that the adenosine-stimulated $I_{SC}$ response is mediated by basolateral to apical $Cl^-$ secretion through a cAMP-dependent $Cl^-$ channel. The rank order of potencies of adenosine receptor agonists was $5'-(N-ethylcarboxamino)adenosine(NECA)＞N^6-(R-phenylisopropyl)adenosine(R-$ PIA)＞2-[p-(2-carbonylethyl)-phenyl-ethylamino]-5'-N-ethylcarboxaminoadenosine(CGS21680). From the above results, it can be concluded that adenosine interacts with the $A_{2b}$ adenosine receptor in the rabbit colon mucosa and a cAMP-dependent signalling mechanism underlies the stimulation of $Cl^-$ secretion.

• 약학회지
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• 제49권2호
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• pp.185-191
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• 2005

The absorption of a P-gp substrate, rhodamine 123, from a liposomal dosage form was investigated across Caco-2 cell monolayers, rat intestines and rat intestinal Peyer's patches in Ussing chamber, Rhodamine 123 was incorporated into liposomes according to the standard evaporation method, which led to a production of liposomes with a mean diameter of 71.3 nm. The permeability (Papp of rhodamine 123 from a water solution across the monolayer was $2.45{\times}10^{-6}$ cm/s for $A{\leftrightarrow}B$ (apical to basal) and $14.0{\times}10^{-6}$ cm/s for $B{\leftrightarrow}A$ (basal to apical) directions, consistent with the fact that rhodamine 123 is one of the P-gp substrates. The transport of rhodamine 123 from the liposomal dosage form was much lower for both directions compared to the solution of rhodamine 123. The transport of rhodamine 123 across the rat intestine was also significantly decreased for both directions, I.e., influx and efflux, by the liposomal incorporation of the compound. The transport of rhodamine 123 across the Peyer's patch was substantially reduced by liposomal incorporation. No difference was found in the transport between the Peyer's patch and non-Peyer's patch. These observations suggest that the contribution of transport via Peyer's patches in the uptake of liposomes may be minimal, especially for rapidly absorbed compounds like rhodamine 123. Therefore, the increased absorption of P-gp substrates does not appear to be feasible by incorporating the compounds in liposomes, due to negligible involvement of Peyer's patches in the uptake of particulate dosage forms like liposomes. Liposomes may rather represent a sustained release dosage form of incorporated compounds.