Shin J M, Besancon M, Prinz C, Simon A, Sachs G
Department of Physiology and Medicine, UCLA.
Aliment Pharmacol Ther. 1994;8 Suppl 1:11-23. doi: 10.1111/j.1365-2036.1994.tb00211.x.
Both receptor antagonists and acid pump inhibitors are clinically useful suppressants of acid secretion. The latter class of drugs, the substituted benzimidazoles, inhibit acid secretion more effectively and, therefore, provide superior symptom relief and healing in all acid-related diseases. The H2-receptor antagonists competitively block the action of histamine on the H2-receptors of parietal cells. This histamine is released from enterochromaffin-like cells (ECL cells) due to gastrin, acetylcholine or epinephrine stimulation. In addition, parietal cells have M3-receptors which can function independently of H2-receptors. Hence, there is no single common pathway for parietal cell stimulation. Stimulation of acid secretion by parietal cells requires activation of the acid pump, the gastric H+,K(+)-ATPase. The target site for the benzimidazoles is the activated gastric H+,K(+)-ATPase, and, in particular, the cysteines of the pump that are exposed to the acid space of the secretory canaliculus of the parietal cells. Pantoprazole in its protonated form selectively reacts with cysteines present in both the fifth and sixth membrane segments of the ATPase, explaining its mechanism of inhibiting proton transport by this enzyme.
受体拮抗剂和酸泵抑制剂都是临床上常用的胃酸分泌抑制剂。后一类药物，即取代苯并咪唑类，能更有效地抑制胃酸分泌，因此在所有与酸相关的疾病中能提供更优的症状缓解和愈合效果。H2受体拮抗剂竞争性阻断组胺对壁细胞H2受体的作用。这种组胺是由胃泌素、乙酰胆碱或肾上腺素刺激肠嗜铬样细胞（ECL细胞）释放的。此外，壁细胞有M3受体，其功能可独立于H2受体。因此，壁细胞刺激不存在单一的共同途径。壁细胞胃酸分泌的刺激需要激活酸泵，即胃H +，K(+)-ATP酶。苯并咪唑类的作用靶点是活化的胃H +，K(+)-ATP酶，特别是该酶中暴露于壁细胞分泌小管酸性空间的半胱氨酸。泮托拉唑的质子化形式选择性地与ATP酶第五和第六个膜段中的半胱氨酸反应，解释了其抑制该酶质子转运的机制。
