2010 Fiscal Year Final Research Report
Systematic analysis of ENS-regulation of drug absorption
| Project/Area Number |
20590145
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Medical pharmacy
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| Research Institution | Okayama University |
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Principal Investigator |
HIGAKI Kazutaka Okayama University, 大学院・医歯薬学総合研究科, 教授 (60284080)
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| Co-Investigator(Kenkyū-buntansha) |
KIMURA Tokishirou 岡山大学, 大学院・医歯薬学総合研究科, 特命教授 (10025710)
OOGAWARA Kenichi 岡山大学, 大学院・医歯薬学総合研究科, 准教授 (30291470)
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| Project Period (FY) |
2008 – 2010
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| Keywords | 腸神経系 / アドレナリン / ベタネコール / 受動拡散 / 細胞間隙経路 / 経細胞経路 / セロトニン / P-糖タンパク質 |
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| Research Abstract |
Effect of enteric nervous system on drug absorption via passive diffusion was investigated with Caco-2 cells monolayer or isolated rat intestinal sheet by utilizing mannitol as a marker for transport through paracellular route and antipyrine and phenacetin as a marker for transport through transcellular route. Stimulation of neither adrenergic neuron nor cholinergic neuron affects the mucosal transport of these small molecules. However, adrenergic stimulation decreased or cholinergic stimulation increased the transport of FD-40 across the intestinal mucosa. On the other hand, model rats of serotonin syndrome were prepared by intraperitoneal injection of both serotonin and clorgyline. Utilizing an isolated intestinal sheet from the model rat, the extensive increase in P-glycoprotein activity was observed, which was at least partly attributed to the significant induction of P-glycoprotein expression.
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