奥美拉唑对离体兔胃腺中胃蛋白酶原合成与分泌的影响。

The influence of omeprazole on the synthesis and secretion of pepsinogen in isolated rabbit gastric glands.

作者信息

Défize J, Pals G, Frants R R, Westerveld B D, Festen H P, Pronk J C, Meuwissen S G, Eriksson A W

出版信息

Biochem Pharmacol. 1985 Oct 15;34(20):3693-9. doi: 10.1016/0006-2952(85)90233-3.

Abstract

Regulation mechanisms of pepsinogen (EC 3.4.23.) synthesis and secretion were studied by following newly synthesized [14C]-labeled pepsinogen during culture of isolated rabbit gastric glands. Omeprazole, a substituted benzimidazole, while almost completely abolishing acid production at 10(-4) M, strongly stimulated secretion of preformed and newly synthesized pepsinogen. Although the pepsinogen synthesis at this concentration of omeprazole was reduced to about 55% of the control rate, a two-fold absolute increase of total secreted pepsinogen was found. This increase was not due to a non specific leakage through disruption of chief cell membranes, as no increase of lactate dehydrogenase in the culture medium could be demonstrated. The stimulated secretion was influenced neither by 10(-3) M cimetidine, 10(-3) sodium thiocyanate nor 10(-4) M atropine. No additivity was found between the carbachol (10(-4) M) or dibutyryl cyclic AMP (10(-3) M) and the omeprazole induced pepsinogen secretion.

摘要

通过在离体兔胃腺培养过程中追踪新合成的[14C]标记胃蛋白酶原，研究了胃蛋白酶原（EC 3.4.23.）合成与分泌的调节机制。奥美拉唑是一种取代苯并咪唑，在10（-4）M时几乎完全抑制胃酸分泌，但强烈刺激预先形成的和新合成的胃蛋白酶原的分泌。尽管在该奥美拉唑浓度下胃蛋白酶原合成降至对照速率的约55%，但发现总分泌胃蛋白酶原有两倍的绝对增加。这种增加并非由于主细胞膜破裂导致的非特异性渗漏，因为培养基中乳酸脱氢酶没有增加。刺激分泌不受10（-3）M西咪替丁、10（-3）硫氰酸钠或10（-4）M阿托品的影响。卡巴胆碱（10（-4）M）或二丁酰环磷腺苷（10（-3）M）与奥美拉唑诱导的胃蛋白酶原分泌之间未发现相加作用。