Regulation of Drug Absorption from Small Intestine by Enteric Nervous System I: a Poorly Absorbable Drug Via Passive Diffusion

• HIGAKI Kazutaka

  Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University

• SONE Miki

  Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University

• OGAWARA Ken-ichi

  Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University

• KIMURA Toshikiro

  Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University

抄録

  To investigate the regulation of drug absorption from the small intestine by the enteric nervous system (ENS), the vascular-luminal perfusion study and the in-vitro transport study were performed by employing phenol red as a poorly absorbable model compound. The effect of ENS on the intestinal absorption of phenol red was examined by adding epinephrine, an adrenergic agonist, or bethanechol, a cholinergic agonist into the vascular perfusate in the vascular-luminal perfused rat small-intestine preparation. The viability of the perfused intestine was checked by the recovery of the vascular perfusate, net water flux and absorbability of antipyrine, a well absorbable drug, and it was confirmed that the function of the perfused small-intestine preparation was maintained for at least 1 hr. The effect of epinephrine or bethanechol on the function of the small intestine was recognized as the increase in net water absorption, or the promotion of the water secretion, respectively. These phenomena are ones that are typically observed when adrenergic or cholinergic neuron is stimulated. Then, we investigated the small-intestinal absorption of phenol red in the vascular-luminal perfused preparation. Absorption clearance (CL_abs) of phenol red was gradually increasing during the perfusion for 1 hr, but the 20-min vascular perfusion with the perfusate containing epinephrine made CL_abs of phenol red constant and significantly lower than those for control study. Furthermore, after the perfusate was changed with the one without any agonist, again, CL_abs of phenol red started to increase. These results clearly indicate that the stimulation of adrenergic neuron by epinephrine leads to the decrease in the small-intestinal absorption of phenol red. On the other hand, the vascular perfusion of bethanechol resulted in the increase in CL_abs of phenol red comparing to the control study. Removing bethanechol from the vascular perfusate decreased CL_abs of phenol red, again. The in-vitro transport study using the isolated jejunum sheet also showed that epinephrine in the serosal solution significantly decreased the transport of phenol red, which can be ascribed to the paracellular pathway tightened by the action of epinephrine because of the increase in transmucosal electrical resistance (TER). On the other hand, although the effect of bethanechol on both the transport of phenol red and TER was not statistically significant, the transport of phenol red tended to increase and the values of TER are smaller than those of control study.<br>

収録刊行物

• Ｄｒｕｇ　Ｍｅｔａｂｏｌｉｓｍ　ａｎｄ　Ｐｈａｒｍａｃｏｋｉｎｅｔｉｃｓ

  Ｄｒｕｇ　Ｍｅｔａｂｏｌｉｓｍ　ａｎｄ　Ｐｈａｒｍａｃｏｋｉｎｅｔｉｃｓ 19 (3), 198-205, 2004

  日本薬物動態学会

キーワード

• enteric nervous system
• adrenergic neuron
• cholinergic neuron
• drug absorption
• vascular-luminal perfused small intestine

詳細情報

• CRID: 1390282680157841536
• NII論文ID: 130004462934
• NII論文ID: 80016771596
• NII書誌ID: AA1162652X
• DOI: 10.2133/dmpk.19.198
• ISSN: 18800920
• ISSN: 13474367
• PubMed: 15499187
• Web Site: http://api.elsevier.com/content/article/PII:S1347436715308193?httpAccept=text/xml
• Web Site: http://api.elsevier.com/content/article/PII:S1347436715308193?httpAccept=text/plain
• Web Site: https://search.jamas.or.jp/link/ui/2005139596
• 本文言語コード: en
• データソース種別:
  • JaLC
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
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