Extremely early onset of ranitidine action on human histamine H2 receptors expressed in HEK293 cells.
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.
Fukushima
Yasushi
Y
Department of Internal Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan. fukusima-tky@umin.ac.jp
Ishikawa
Takashi
T
Saitoh
Toshihito
T
Tateishi
Keisuke
K
Ogihara
Takehide
T
Fujishiro
Midori
M
Shojima
Nobuhiro
N
Honda
Miho
M
Kushiyama
Akifumi
A
Anai
Motonobu
M
Sakoda
Hideyuki
H
Ono
Hiraku
H
Onishi
Yukiko
Y
Otsuka
Hiroko
H
Katagiri
Hideki
H
Nagai
Ryozo
R
Omata
Masao
M
Asano
Tomoichiro
T
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
D000897:Anti-Ulcer Agents; D006635:Histamine H2 Antagonists; D011970:Receptors, Histamine H2; D015738:Famotidine; D011899:Ranitidine; D000242:Cyclic AMP