An aqueous extract of Poncirus fructus activates the prokinetic activity of 5-HT receptor subtype 4 without hERG interaction.
J Ethnopharmacol
; 132(1): 328-33, 2010 Oct 28.
Article
in En
| MEDLINE
| ID: mdl-20736054
ABSTRACT
AIM OF THE STUDY Poncirus fructus (PF)--also known as the dried, immature fruit of Poncirus trifoliata (L.) Raf. (Rutaceae)--is a natural substance that has long been used for various gastrointestinal disorders in eastern Asia. An aqueous extract of PF (PF-W) has particularly potent gastroprokinetic effects, but its molecular mechanism was not well understood. Identification of the underlying prokinetic mechanism of PF-W was pursued in the present study. MATERIALS AND METHODS:
Changes in in vitro cAMP levels and in vivo intestinal transit rate (ITR) caused by PF-W were measured after pretreatment with GR125487, an antagonist for serotonin receptor subtype 4 (5-HT4R). An [(3)H] astemizole binding assay and electrophysiology experiments were performed to determine if PF-W has any interaction with the human ether-à-go-go related gene (hERG) potassium channel.RESULTS:
PF-W induced an increase in intracellular cAMP in 5-HT4R-expressing HEK293T cells, indicating that PF-W does activate 5-HT4R. Moreover, pretreatment with GR125487 successfully blocked the increase, suggesting that the response was 5-HT4R-specific. More importantly, pretreatment of GR125487 in rats inhibited the elevation of ITR by PF-W, indicating that the prokinetic effect of PF-W was indeed exerted via 5-HT4R. On the other hand, both [(3)H]-astemizole binding assay and electrophysiological experiments revealed that PF-W did not interfere at all with the hERG channel.CONCLUSION:
It was found that PF-W exerts its prokinetic activity through a 5-HT4R-mediated pathway, with no interaction with hERG channels. Therefore, PF-W is a good candidate that might be developed as a prokinetic agent with fewer expected cardiac side effects.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Gastrointestinal Transit
/
Plant Extracts
/
Poncirus
/
Receptors, Serotonin, 5-HT4
/
Ether-A-Go-Go Potassium Channels
/
Serotonin 5-HT4 Receptor Agonists
Limits:
Animals
/
Humans
Language:
En
Journal:
J Ethnopharmacol
Year:
2010
Document type:
Article