title: Ghrelin receptor is activated by naringin and naringenin, constituents of a prokinetic agent Poncirus fructus.
abstract: BACKGROUND
  Poncirus fructus (PF), also known as a dried immature fruit of Poncirus trifoliata (L.) Raf. (Rutaceae), has long been traditionally used for the various gastrointestinal disorders in Eastern Asia.
  
  
  OBJECTIVE
  The aqueous extract of PF (PF-W) has the strong prokinetic effect, yet the underlying mechanism is still elusive. The present study investigated whether PF-W has any effect on motilin receptor or ghrelin receptor, since these receptors enhance intestinal motility when activated.
  
  
  METHODS
  The effect of PF-W and its components on motilin or ghrelin receptor was determined by calcium imaging and whole-cell patch clamp methods.
  
  
  RESULTS
  PF-W activates the ghrelin receptor, but not the motilin receptor, resulting in a transient increase of intracellular calcium levels. Furthermore, among various constituents of PF, only naringin and naringenin evoked the intracellular calcium augmentation via the ghrelin receptor. Moreover, cortistatin-8 - a ghrelin receptor inhibitor - specifically blocked naringin- and naringenin-induced calcium increases. In addition, naringin and naringenin induced inward currents in ghrelin receptor-expressing cells under whole-cell patch clamp configuration.
  
  
  CONCLUSIONS
  PF-W activates the ghrelin receptor, and naringin and naringenin are key constituents responsible for the activation of ghrelin receptor. Therefore, the present study suggests that the ghrelin receptor is a molecular entity responsible for the strong prokinetic activity of PF-W.
authors: College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-742, Republic of Korea.
authors: Yongwoo
authors: Y
authors: Jang
authors: Su-Won
authors: SW
authors: Kim
authors: Jungeun
authors: J
authors: Oh
authors: Gyu-Sang
authors: GS
authors: Hong
authors: Eun-Kyoung
authors: EK
authors: Seo
authors: Uhtaek
authors: U
authors: Oh
authors: Won-Sik
authors: WS
authors: Shim
mesh_terms: D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D044950:Flavanones / Q000494:pharmacology*; D005638:Fruit / Q000737:chemistry; D005765:Gastrointestinal Agents / Q000737:chemistry* / Q000494:pharmacology*; D005769:Gastrointestinal Motility / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D009479:Neuropeptides / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology; D032104:Poncirus / Q000737:chemistry*; D011964:Receptors, Gastrointestinal Hormone / Q000378:metabolism; D054440:Receptors, Ghrelin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018013:Receptors, Neuropeptide / Q000378:metabolism; D027821:Rutaceae / Q000737:chemistry*; D014867:Water / Q000737:chemistry
chemical_list: D044950:Flavanones; D005765:Gastrointestinal Agents; D009479:Neuropeptides; D010936:Plant Extracts; D011964:Receptors, Gastrointestinal Hormone; D054440:Receptors, Ghrelin; D018013:Receptors, Neuropeptide; C528326:cortistatin-8; C050802:motilin receptor; D014867:Water; D000242:Cyclic AMP; C005273:naringenin; C005274:naringin; D002118:Calcium