Ishikawa T, Kamisaki Y, Itoh T
Department of Clinical Pharmacology, Tottori University School of Medicine, Yonago, Japan.
Agents Actions. 1989 Mar;26(3-4):261-6. doi: 10.1007/BF01967288.
The pharmacological effects of the beta-hydroxylated histamine, 4(5)-(2-amino-1-hydroxyethyl)-imidazole, on smooth muscle contraction of the ileum (H1-receptor activity) and gastric acid secretion (H2-receptor activity) of the guinea-pig were investigated and compared with those of histamine. Although beta-hydroxy histamine contracted the ileum with the same maximal response as histamine, the concentration response curve was shifted to the right by approximately three orders of magnitude. At submaximal concentrations, co-administration of beta-hydroxy histamine with histamine revealed only additive effects. This H1-activity was competitively inhibited by diphenhydramine. Similarly, the hydroxylated analogue also increased intracellular cyclic AMP level and [14C] aminopyrine accumulation as a marker of acid secretion in the parietal cells. However, the EC50 was approximately ten fold that of histamine. This H2-receptor activity was inhibited completely by cimetidine. These results suggest that beta-hydroxy histamine possesses nearly full intrinsic activities at both H1 and H2-receptors and that the introduction of a hydroxyl group at the beta-carbon reduces and dissociates these activities.
研究了β-羟基化组胺4(5)-(2-氨基-1-羟乙基)-咪唑对豚鼠回肠平滑肌收缩（H1受体活性）和胃酸分泌（H2受体活性）的药理作用，并与组胺进行了比较。虽然β-羟基组胺使回肠收缩，其最大反应与组胺相同，但浓度-反应曲线向右移动了约三个数量级。在亚最大浓度下，β-羟基组胺与组胺共同给药仅显示相加作用。这种H1活性被苯海拉明竞争性抑制。同样，羟基化类似物也增加了细胞内环状AMP水平以及作为壁细胞酸分泌标志物的[14C]氨基比林蓄积。然而，其半数有效浓度（EC50）约为组胺的10倍。这种H2受体活性被西咪替丁完全抑制。这些结果表明，β-羟基组胺在H1和H2受体上均具有几乎完全的内在活性，并且在β-碳上引入羟基会降低并使这些活性解离。
