Dockray G J, Hamer C, Evans D, Varro A, Dimaline R
Department of Physiology, University of Liverpool, England.
Gastroenterology. 1991 May;100(5 Pt 1):1187-94.
Prolonged achlorhydria leads to hypergastrinemia which must be matched by increased gastrin production. The extent to which the balance between synthesis and storage or secretion is shifted in achlorhydria remains uncertain. In the present study, rats were treated for 14 days with the hydrogen-potassium-stimulated ATPase inhibitor omeprazole, and the effects on plasma and tissue gastrin concentrations and on the abundance of gastrin messenger RNA were examined. To calculate the fractional release rates of gastrin, the metabolic clearance rate of synthetic unsulfated rat heptadeca peptide gastrin in anesthetized rats was also measured. Treatment with omeprazole for 14 days led to a profound hypergastrinemia, a twofold increase in antral gastrin stores, and a tenfold increase in messenger RNA. Calculations based on the metabolic clearance rate for rat heptadecapeptide gastrin suggested that in control rats, about 0.08% of stored gastrin was released per minute compared with about 0.4% in omeprazole-treated rats. No evidence was observed to suggest that changes in the efficiency of conversion of Gly-extended gastrins to amidated peptides were of any significance in accounting for the increased production of amidated gastrin. The increased gastrin synthesis in achlorhydria is therefore attributable to increased messenger RNA levels; most of the increase in gastrin production is directly secreted as changes in the stores of gastrin appear to be of lesser importance.
长期胃酸缺乏会导致高胃泌素血症，这必然伴随着胃泌素分泌增加。胃酸缺乏时，胃泌素合成、储存与分泌之间的平衡发生何种程度的变化仍不确定。在本研究中，用氢钾刺激的ATP酶抑制剂奥美拉唑对大鼠进行14天治疗，检测其对血浆和组织胃泌素浓度以及胃泌素信使核糖核酸丰度的影响。为计算胃泌素的分数释放率，还测定了麻醉大鼠体内合成的未硫酸化大鼠十七肽胃泌素的代谢清除率。用奥美拉唑治疗14天导致严重的高胃泌素血症，胃窦胃泌素储存量增加两倍，信使核糖核酸增加十倍。根据大鼠十七肽胃泌素的代谢清除率计算表明，对照大鼠中，每分钟约0.08%的储存胃泌素被释放，而在奥美拉唑治疗的大鼠中约为0.4%。未观察到证据表明甘氨酸延伸型胃泌素转化为酰胺化肽的效率变化在解释酰胺化胃泌素产量增加方面具有任何意义。因此，胃酸缺乏时胃泌素合成增加归因于信使核糖核酸水平升高；胃泌素产量增加大多直接分泌，因为胃泌素储存量的变化似乎不太重要。
