N-α-甲基组胺对CHO细胞中表达的人H(2)受体的作用。
Effects of N-alpha-methyl-histamine on human H(2) receptors expressed in CHO cells.
作者信息
Saitoh T, Fukushima Y, Otsuka H, Ishikawa M, Tamai M, Takahashi H, Mori H, Asano T, Anai M, Ishikawa T, Katsube T, Ogawa K, Kajiwara T, Omata M, Ohkawa S
机构信息
Department of Internal Medicine, Tokyo Women's Medical University Daini Hospital, 2-1-10 Nishiogu, Arakawa-ku, Tokyo 116-8567, Japan.
出版信息
Gut. 2002 Jun;50(6):786-9. doi: 10.1136/gut.50.6.786.
BACKGROUND
Production of N-alpha-methyl-histamine (NAMH), a histamine H(3) receptor (H3R) agonist, is reportedly promoted in Helicobacter pylori infected human gastric mucosa. NAMH was suggested to act directly on histamine H(2) 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 EC(50) concentration and higher maximal cAMP production. Both NAMH and histamine, but not R-alpha-methyl-histamine, effectively inhibited [(3)H] 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.
背景
据报道，在幽门螺杆菌感染的人胃黏膜中，组胺H3受体（H3R）激动剂N-α-甲基组胺（NAMH）的生成会增加。据推测，NAMH在动物体内可直接作用于组胺H2受体（H2R）以刺激胃酸分泌，是一种H2R激动剂。由于H2R和H3R在胃酸分泌中发挥不同作用，因此验证NAMH是否为H2R激动剂非常重要。
目的
确定NAMH是否为H2R激动剂以及H3R激动剂。
方法
我们使用表达人H2R的中国仓鼠卵巢（CHO）细胞系（CHO-H2R）和对照CHO细胞。通过替丁 binding 确认人H2R的表达。测量CHO-H2R和对照细胞中组胺或NAMH刺激后的环磷酸腺苷（cAMP）生成。在存在或不存在H2R拮抗剂法莫替丁和H3R拮抗剂硫代哌酰胺的情况下，也测量了对10⁻⁷ M NAMH的cAMP生成。
结果
NAMH剂量依赖性地刺激CHO-H2R细胞中的cAMP生成。这种生成受到法莫替丁的抑制，但不受硫代哌酰胺的抑制。对照CHO细胞对组胺或NAMH均无反应。此外，就CHO-H2R细胞中的cAMP生成而言，NAMH的作用比组胺更强，即具有更低的半数有效浓度（EC50）和更高的最大cAMP生成量。NAMH和组胺均可有效抑制[³H]替丁与CHO-H2R细胞的结合，但R-α-甲基组胺则无此作用。
结论
幽门螺杆菌在胃黏膜中产生的NAMH是一种强效的H2R激动剂以及H3R激动剂。
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