Role of histamine2 receptor in increased expression of rat gastric H(+)-K(+)-ATPase alpha-subunit induced by omeprazole.
Role of histamine2 receptor in increased expression of rat gastric H(+)-K(+)-ATPase alpha-subunit induced by omeprazole.
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组胺2受体在奥美拉唑诱导的大鼠胃H()-K()-ATP酶α亚基表达增加中的作用。
DOI：
10.1152/ajpgi.1993.265.4.g752
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Walsh,JH
中科院分区：
文献类型：
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作者：
Tari,A;Yamamoto,G;Sumii,K;Sumii,M;Takehara,Y;Haruma,K;Kajiyama,G;Wu,V;Sachs,G;Walsh,JH
奥美拉唑在体内是壁细胞分泌小管中具有功能的胃酸泵H(+)-K(+)-腺苷三磷酸酶（atp酶）的特异性抑制剂。先前有研究表明，奥美拉唑在大鼠体内导致H(+)-K(+)- atp酶α亚基mRNA的增加。奥美拉唑引起该物种循环胃泌素的显著增加，这反过来刺激肠嗜铬细胞释放组胺。这一途径的可能作用是通过体内给药法莫替丁（一种有效的H2受体拮抗剂）来研究的。单次腹腔注射法莫替丁（200mg /kg）可导致短暂性高胃泌素血症，在3小时达到峰值，12小时恢复正常，抑制分泌持续12小时，但α -亚基mRNA或β -肌动蛋白mRNA水平未发生变化。相比之下，单剂量奥美拉唑（x = 100 mg/kg）抑制胃酸分泌并产生高胃泌素血症，在12 h达到峰值，这两种作用持续24小时的观察期。奥美拉唑在3 h时使α -亚单位mRNA瞬间升高3倍以上，24 h时恢复正常水平。奥美拉唑后1 h给予法莫替丁未改变奥美拉唑对胃酸分泌的影响，但进一步升高了胃泌素水平。α -亚基mRNA在前6小时没有升高，但在12小时有小幅升高，在24小时进一步增加到约2.5倍。
Omeprazole is a specific inhibitor in vivo of the functioning gastric acid pump, the H(+)-K(+)-adenosinetriphosphatase (ATPase), in the secretory canaliculus of the parietal cell. It has been shown previously that omeprazole in rats led to an increase in the mRNA for the alpha-subunit of the H(+)-K(+)-ATPase. Omeprazole causes a marked increase in circulating gastrin in this species, which in turn stimulates release of histamine from the enterochromaffin-like cell. The possible role of this pathway was investigated by the in vivo administration of famotidine, a potent H2 receptor antagonist. A single intraperitoneal dose of famotidine, 200 mg/kg, produced a transient hypergastrinemia peaking at 3 h and normalizing at 12 h, inhibition of secretion that lasted for 12 h, but no change in the level of the alpha-subunit mRNA or of beta-actin mRNA. In contrast, a single dose of omeprazole,xs 100 mg/kg, inhibited acid secretion and produced hypergastrinemia, peaking at 12 h, both effects lasting for the 24-h observation period. Omeprazole elevated the alpha-subunit mRNA transiently by more than threefold at 3 h, with normal levels being restored at 24 h. The administration of famotidine 1 h after omeprazole did not change the effects of omeprazole on acid secretion but elevated the gastrin levels further. There was now no elevation of the alpha-subunit mRNA for the first 6 h, but a small increase at 12 h and a further increase to approximately 2.5-fold at 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)