Effect of adrenergic stimulation on drug absorption via passive diffusion in Caco-2 cells

Takahiro Kimoto, Masashi Takanashi, Hironori Mukai, Ken-ichi Ogawara, Toshikiro Kimura, Kazutaka Higaki

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)


It is well known that the enteric nervous system (ENS) regulates the movement and function of the small intestine, but the effects of ENS on drug absorption from the small intestine still remain to be clarified. Focusing on adrenergic effect, we tried to evaluate how adrenergic stimulation influences the drug absorption via passive diffusion using Caco-2 cells as model epithelial cells, a terminal effector of ENS. Adrenaline, an adrenergic agonist, did not affect the transport of small molecules such as antipyrine, phenacetin and mannitol, but decreased the transport of large molecules such as FITC-dextran (FD)-20 and FD-40 without transepithelial electrical resistance (TEER) change. These results suggested that the transport of large molecules via paracellular route would be attenuated by adrenergic stimulation. Only clonidine, an α2-agonist, among selective adrenoceptor agonists decreased FD-40 transport across Caco-2 cell monolayers and the agonist also decreased intracellular cAMP. Furthermore, H-89, a protein kinase A inhibitor, significantly decreased FD-40 transport and dibutyryl cAMP, a cAMP derivative, increased it. These results suggest that the decrease in FD-40 transport would be mainly attributed to the decrease in intracellular cAMP and subsequent decrease in PKA activity via α2-receptor stimulation.

Original languageEnglish
Pages (from-to)31-36
Number of pages6
JournalInternational Journal of Pharmaceutics
Issue number1-2
Publication statusPublished - Feb 23 2009


  • Adrenaline
  • Adrenoceptor
  • Clonidine
  • Enteric nervous system
  • Paracellular transport
  • Passive diffusion

ASJC Scopus subject areas

  • Pharmaceutical Science


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