Mårdh S, Song Y H, Wallmark B
Dept. of Medical and Physiological Chemistry, Uppsala University, Sweden.
Scand J Gastroenterol. 1988 Oct;23(8):977-82. doi: 10.3109/00365528809090157.
The effects of some inhibitors of acid secretion were tested on isolated, purified pig parietal cells. The cells were stimulated with 10(-4) M histamine, 10(-5) M carbachol, or 10(-7) M pentagastrin. The H,K-ATPase inhibitors SCH 28080 and omeprazole inhibited both the basal and secretagogue-stimulated acid production, as measured by aminopyrine accumulation, irrespective of the type of stimulator used. The IC50 value was 3-5 x 10(-9) M for SCH 28080 and 1-3 x 10(-8) M for omeprazole. Ranitidine inhibited the histamine-stimulated but not the basal acid production. The IC50 value was 2 x 10(-5) M. Stimulation of acid production with carbachol was blocked by pirenzepine, with an IC50 of 6 x 10(-7) M. Pirenzepine (10(-5) M) specifically blocked the carbachol-stimulated increase in cytosolic free Ca2+ in fura-2-loaded cells but not the increase in cytosolic free Ca2+ induced by histamine or pentagastrin. Ranitidine (10(-4) M) prevented the histamine-induced increase in Ca2+ and was also the only one of the four inhibitors which prevented the histamine-stimulated cAMP formation. SCH 28080 (10(-5) M) significantly potentiated the histamine-stimulated increase in cytosolic free Ca2+ and the formation of cAMP, whereas omeprazole (10(-5) M) was without effect.
在分离纯化的猪壁细胞上测试了一些胃酸分泌抑制剂的作用。用10⁻⁴M组胺、10⁻⁵M卡巴胆碱或10⁻⁷M五肽胃泌素刺激细胞。通过氨基比林蓄积测定，H⁺，K⁺ - ATP酶抑制剂SCH 28080和奥美拉唑抑制基础胃酸分泌以及促分泌剂刺激的胃酸分泌，与所用刺激剂的类型无关。SCH 28080的IC50值为3 - 5×10⁻⁹M，奥美拉唑的IC50值为1 - 3×10⁻⁸M。雷尼替丁抑制组胺刺激的胃酸分泌，但不抑制基础胃酸分泌。IC50值为2×10⁻⁵M。哌仑西平可阻断卡巴胆碱刺激的胃酸分泌，IC50为6×10⁻⁷M。哌仑西平（10⁻⁵M）特异性阻断卡巴胆碱刺激的、用fura - 2负载的细胞中胞质游离Ca²⁺的增加，但不阻断组胺或五肽胃泌素诱导的胞质游离Ca²⁺的增加。雷尼替丁（10⁻⁴M）可阻止组胺诱导的Ca²⁺增加，并且是四种抑制剂中唯一能阻止组胺刺激的cAMP形成的药物。SCH 28080（10⁻⁵M）显著增强组胺刺激的胞质游离Ca²⁺增加和cAMP形成，而奥美拉唑（10⁻⁵M）则无此作用。
