title: Extremely early onset of ranitidine action on human histamine H2 receptors expressed in HEK293 cells.
abstract: OBJECTIVE
  Histamine H2 receptor antagonists are considered to exert their effects on gastric acid secretion more rapidly than proton pump antagonists. However, there are no reports concerning the direct interaction of a histamine H2 receptor antagonist with the human H2 receptor in terms of onset of action. This study aims to characterize how rapidly famotidine and ranitidine, the most widely used histamine H2 receptor antagonists, interact with the human histamine H2 receptor.
  
  
  METHODS
  HEK293 cell lines, stably expressing human histamine H2 receptors, were obtained. The dose- and time-dependent effects of famotidine and ranitidine on [3H]-tiotidine binding and histamine-stimulated cAMP production were analyzed.
  
  
  RESULTS
  Ranitidine inhibited both [3H]-tiotidine binding and histamine-stimulated cAMP production more promptly than did famotidine. Inhibition of histamine-stimulated cAMP production by Cmax doses of famotidine (20 mg p.o.) and ranitidine (150 mg p.o.) peaked by 15 and 2 min, respectively. [3H]-tiotidine binding was not saturated by 60 min at the famotidine Cmax, while the ranitidine Cmax had produced saturation by 15 min.
  
  
  CONCLUSIONS
  Ranitidine inhibits the human histamine H2 receptor very rapidly.
authors.affiliation: Department of Internal Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan. fukusima-tky@umin.ac.jp
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Fukushima
authors.forename: Takashi
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Toshihito
authors.initials: T
authors.lastname: Saitoh
authors.forename: Keisuke
authors.initials: K
authors.lastname: Tateishi
authors.forename: Takehide
authors.initials: T
authors.lastname: Ogihara
authors.forename: Midori
authors.initials: M
authors.lastname: Fujishiro
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Shojima
authors.forename: Miho
authors.initials: M
authors.lastname: Honda
authors.forename: Akifumi
authors.initials: A
authors.lastname: Kushiyama
authors.forename: Motonobu
authors.initials: M
authors.lastname: Anai
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Sakoda
authors.forename: Hiraku
authors.initials: H
authors.lastname: Ono
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Onishi
authors.forename: Hiroko
authors.initials: H
authors.lastname: Otsuka
authors.forename: Hideki
authors.initials: H
authors.lastname: Katagiri
authors.forename: Ryozo
authors.initials: R
authors.lastname: Nagai
authors.forename: Masao
authors.initials: M
authors.lastname: Omata
authors.forename: Tomoichiro
authors.initials: T
authors.lastname: Asano
mesh_terms: D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D015738:Famotidine / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D006801:Humans; D011899:Ranitidine / Q000494:pharmacology*; D011970:Receptors, Histamine H2 / Q000187:drug effects*; D018709:Statistics, Nonparametric; D013997:Time Factors
chemical_list: D000897:Anti-Ulcer Agents; D006635:Histamine H2 Antagonists; D011970:Receptors, Histamine H2; D015738:Famotidine; D011899:Ranitidine; D000242:Cyclic AMP