RT Journal Article
SR Electronic
T1 Effects of <em>N</em>-alpha-methyl-histamine on human H<sub>2</sub> receptors expressed in CHO cells
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 786
OP 789
DO 10.1136/gut.50.6.786
VO 50
IS 6
A1 T Saitoh
A1 Y Fukushima
A1 H Otsuka
A1 M Ishikawa
A1 M Tamai
A1 H Takahashi
A1 H Mori
A1 T Asano
A1 M Anai
A1 T Ishikawa
A1 T Katsube
A1 K Ogawa
A1 T Kajiwara
A1 M Omata
A1 S Ohkawa
YR 2002
UL http://gut.bmj.com/content/50/6/786.abstract
AB Background: Production of N-alpha-methyl-histamine (NAMH), a histamine H3 receptor (H3R) agonist, is reportedly promoted in Helicobacter pylori infected human gastric mucosa. NAMH was suggested to act directly on histamine H2 receptors (H2Rs) in animals to stimulate acid secretion and to be a H2R agonist. As H2Rs and H3Rs play different roles in gastric acid secretion, it is very important to verify that NAMH is a H2R agonist. Aims: To determine whether NAMH is a H2R agonist, as well as a H3R agonist. Methods: We used a Chinese hamster ovary (CHO) cell line expressing human H2Rs (CHO-H2R) and control CHO cells. Expression of human H2Rs was confirmed by tiotidine binding. cAMP production in CHO-H2R and control cells in response to histamine or NAMH was measured. cAMP production in response to 10−7 M NAMH was also measured in the presence or absence of the H2R antagonist famotidine and the H3R antagonist thioperamide. Results: NAMH dose dependently stimulated cAMP productions in CHO-H2R cells. This production was inhibited by famotidine but not by thioperamide. Control CHO cells were unresponsive to either histamine or NAMH. In addition, the effect of NAMH, in terms of cAMP production in CHO-H2R cells, was more potent than that of histamine—that is, with a lower EC50 concentration and higher maximal cAMP production. Both NAMH and histamine, but not R-alpha-methyl-histamine, effectively inhibited [3H] tiotidine binding to CHO-H2R cells. Conclusions: NAMH, which is produced in the gastric mucosa by H pylori, is a potent H2R agonist as well as a H3R agonist.