Linked Life Data

12499649

Source:http://linkedlifedata.com/resource/pubmed/id/12499649

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2002-12-24
pubmed:abstractText
The aims of this study were to examine the enhancing effects of aloe-emodin anthrone (AEA) on the colonic membrane permeability of water-soluble and poorly permeable compounds and to clarify the mechanism of the permeation-enhancing activity of AEA. The permeation-enhancing activity of AEA was estimated from changes in the permeability coefficient of 5(6)-carboxyfluorescein (CF) in rat colonic mucosa using a Ussing-type chamber. Various inhibitors were used to investigate the mechanism of action of AEA. The structural change in the membrane and the cytotoxicity of AEA in the intestinal mucosa were evaluated by measuring the electrical resistance of the membrane (R(m)) and lactate dehydrogenase (LDH) activity, respectively. AEA significantly increased the permeation of CF in a dose-dependent manner. The enhanced permeability was significantly suppressed by a histamine H(1) receptor antagonist, pyrilamine, and a mast cell stabilizer, ketotifen, but not by a histamine H(2) receptor antagonist, cimetidine. The enhancing effect was also inhibited by an inhibitor of protein kinase C (PKC). Potential difference and short-circuit current values decreased, while R(m) values remained constant throughout the experiment. The addition of AEA to the mucosal solution decreased R(m) to 30%, but then remained constant. LDH activity with AEA was not significantly different from that of the control. In conclusion, AEA is a candidate for effective absorption enhancers without damage of the membrane and cytotoxicity. We propose that AEA stimulates mast cells within the colonic mucosa to release histamine, which probably bind to the H(1) receptor. The intracellular PKC route activated by H(1) receptor activation enhances the permeability of water-soluble and poorly permeable drugs via opening of tight junctions in rat colonic membrane.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0918-6158
pubmed:author
pubmed:issnType
Print
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1608-13
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Permeation-enhancing effect of aloe-emodin anthrone on water-soluble and poorly permeable compounds in rat colonic mucosa.
pubmed:affiliation
Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Japan.
pubmed:publicationType
Journal Article, In Vitro