Up-regulation of P-glycoprotein expression in small intestine under chronic serotonin-depleted conditions in rats

Hideo Hiraoka, Naoji Kimura, Yumiko Furukawa, Ken Ichi Ogawara, Toshikiro Kimura, Kazutaka Higaki

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

To investigate the role of serotonin (5-HT), an important neurotransmitter and hormone/paracrine agent in the small intestine, in the transport activity of P-glycoprotein (P-gp), the intestinal transport of quinidine, a P-gp substrate, was examined in 5-HT-depleted rats prepared by intraperitoneal administration of p-chlorophenylalanine, a specific inhibitor of tryptophan hydroxylase in 5-HT biosynthesis. In the in vitro transport study, quinidine transport across rat jejunum was significantly enhanced in both the secretory and absorptive directions under 5-HT-depleted conditions, although the secretory transport was still predominant. The electrophysiological study suggested that the quinidine transport via passive diffusion was enhanced presumably through a paracellular route. This might be due to looser tight junctions under 5-HT-depleted conditions. The voltage-clamp technique clearly indicated that the secretory transport of quinidine through the transcellular pathway was also enhanced by the depletion of 5-HT. Furthermore, 5-HT depletion increased verapamil-sensitive secretory transport of quinidine in rat jejunum. These results indicate that the secretory transport of quinidine via P-gp was significantly enhanced under 5-HT-depleted conditions. The level of ATP, an energy source for functioning P-gp, wet weight of jejunum, and total protein level in rat jejunal mucosa were not changed by 5-HT depletion, but the expression of P-gp in the brush-border membrane of rat jejunum was significantly induced, which is partly responsible for the enhancement of P-gp activity under the 5-HT-depleted condition.

Original languageEnglish
Pages (from-to)248-255
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume312
Issue number1
DOIs
Publication statusPublished - Jan 1 2005

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Fingerprint Dive into the research topics of 'Up-regulation of P-glycoprotein expression in small intestine under chronic serotonin-depleted conditions in rats'. Together they form a unique fingerprint.

  • Cite this