Abstract
The effects of nitric oxide (NO) donors NOC5 [3-(2-hydroxy-1-(methylethyl)-2-nitrosohydrazino)-1-propanamine] and NOC12 [N-ethyl-2-(1-ethyl-hydroxy-2-nitrosohydrazino)-ethanamine] on the permeability of 5(6)-carboxyfluorescein (CF) across the intestinal membrane were examined by an in vitro using chamber method. The NO donors significantly increased the intestinal permeability of CF and their absorption-enhancing effects were concentration-dependent over the range of 0.01 to 0.1 mM. Regional differences in the absorption-enhancing effects of the NO donors were observed (colon > jejunum). The absorption-enhancing effect of NOC12 reduced as the molecular weights of compounds increased. Therefore, the degree of absorption-enhancing effect of NOC12 was dependent on the molecular weights of compounds. In the pretreatment studies with NOC12 and lactate dehydrogenase release studies, the absorption-enhancing effect of 0.1 mM NOC12 was reversible and less toxic to the colonic membrane. On the other hand, the absorption-enhancing effect of NOC12 was inhibited by the coadministration of 2-(4-carboxyphenyl) 4,4,5,5-tetramethylimidazole-1-oxyl 3-oxide sodium salt, an NO scavenger, suggesting that NO can regulate the permeability of water-soluble drugs in the gut. Furthermore, NOC12 (0.1 and 1 mM) significantly decreased the transepithelial electrical resistance value of the colonic membrane, suggesting that the absorptionenhancing mechanism of NOC12 may be partly related to the dilation of the tight junction in the epithelium via a paracellular route. These findings suggest that NO donors may be useful to enhance the intestinal absorption of poorly absorbable drugs.
| Original language | English |
|---|---|
| Pages (from-to) | 84-90 |
| Number of pages | 7 |
| Journal | Journal of Pharmacology and Experimental Therapeutics |
| Volume | 296 |
| Issue number | 1 |
| Publication status | Published - Jan 11 2001 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Pharmacology
Cite this
Modulation of intestinal permeability by nitric oxide donors : Implications in intestinal delivery of poorly absorbable drugs. / Yamamoto, Akira; Tatsumi, Hiroyuki; Maruyama, Masato; Uchiyama, Tomomi; Okada, Naoki; Fujita, Takuya.
In: Journal of Pharmacology and Experimental Therapeutics, Vol. 296, No. 1, 11.01.2001, p. 84-90.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Modulation of intestinal permeability by nitric oxide donors
T2 - Implications in intestinal delivery of poorly absorbable drugs
AU - Yamamoto, Akira
AU - Tatsumi, Hiroyuki
AU - Maruyama, Masato
AU - Uchiyama, Tomomi
AU - Okada, Naoki
AU - Fujita, Takuya
PY - 2001/1/11
Y1 - 2001/1/11
N2 - The effects of nitric oxide (NO) donors NOC5 [3-(2-hydroxy-1-(methylethyl)-2-nitrosohydrazino)-1-propanamine] and NOC12 [N-ethyl-2-(1-ethyl-hydroxy-2-nitrosohydrazino)-ethanamine] on the permeability of 5(6)-carboxyfluorescein (CF) across the intestinal membrane were examined by an in vitro using chamber method. The NO donors significantly increased the intestinal permeability of CF and their absorption-enhancing effects were concentration-dependent over the range of 0.01 to 0.1 mM. Regional differences in the absorption-enhancing effects of the NO donors were observed (colon > jejunum). The absorption-enhancing effect of NOC12 reduced as the molecular weights of compounds increased. Therefore, the degree of absorption-enhancing effect of NOC12 was dependent on the molecular weights of compounds. In the pretreatment studies with NOC12 and lactate dehydrogenase release studies, the absorption-enhancing effect of 0.1 mM NOC12 was reversible and less toxic to the colonic membrane. On the other hand, the absorption-enhancing effect of NOC12 was inhibited by the coadministration of 2-(4-carboxyphenyl) 4,4,5,5-tetramethylimidazole-1-oxyl 3-oxide sodium salt, an NO scavenger, suggesting that NO can regulate the permeability of water-soluble drugs in the gut. Furthermore, NOC12 (0.1 and 1 mM) significantly decreased the transepithelial electrical resistance value of the colonic membrane, suggesting that the absorptionenhancing mechanism of NOC12 may be partly related to the dilation of the tight junction in the epithelium via a paracellular route. These findings suggest that NO donors may be useful to enhance the intestinal absorption of poorly absorbable drugs.
AB - The effects of nitric oxide (NO) donors NOC5 [3-(2-hydroxy-1-(methylethyl)-2-nitrosohydrazino)-1-propanamine] and NOC12 [N-ethyl-2-(1-ethyl-hydroxy-2-nitrosohydrazino)-ethanamine] on the permeability of 5(6)-carboxyfluorescein (CF) across the intestinal membrane were examined by an in vitro using chamber method. The NO donors significantly increased the intestinal permeability of CF and their absorption-enhancing effects were concentration-dependent over the range of 0.01 to 0.1 mM. Regional differences in the absorption-enhancing effects of the NO donors were observed (colon > jejunum). The absorption-enhancing effect of NOC12 reduced as the molecular weights of compounds increased. Therefore, the degree of absorption-enhancing effect of NOC12 was dependent on the molecular weights of compounds. In the pretreatment studies with NOC12 and lactate dehydrogenase release studies, the absorption-enhancing effect of 0.1 mM NOC12 was reversible and less toxic to the colonic membrane. On the other hand, the absorption-enhancing effect of NOC12 was inhibited by the coadministration of 2-(4-carboxyphenyl) 4,4,5,5-tetramethylimidazole-1-oxyl 3-oxide sodium salt, an NO scavenger, suggesting that NO can regulate the permeability of water-soluble drugs in the gut. Furthermore, NOC12 (0.1 and 1 mM) significantly decreased the transepithelial electrical resistance value of the colonic membrane, suggesting that the absorptionenhancing mechanism of NOC12 may be partly related to the dilation of the tight junction in the epithelium via a paracellular route. These findings suggest that NO donors may be useful to enhance the intestinal absorption of poorly absorbable drugs.
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M3 - Article
C2 - 11123366
AN - SCOPUS:0035198046
VL - 296
SP - 84
EP - 90
JO - Journal of Pharmacology and Experimental Therapeutics
JF - Journal of Pharmacology and Experimental Therapeutics
SN - 0022-3565
IS - 1
ER -