Brown J F, Hanson P J, Whittle B J
Pharmaceutical Sciences Institute, Aston University, Triangle, Birmingham, UK.
Biochem Biophys Res Commun. 1993 Sep 30;195(3):1354-9. doi: 10.1006/bbrc.1993.2192.
Accumulation of the weak base aminopyrine was used as an index of acid secretory activity in rat isolated parietal cells. The nitric oxide (NO) donor, S-nitroso-N-acetyl-penicillamine (SNAP) caused a dose-dependent inhibition of aminopyrine accumulation (half-maximally effective concentration 247 microM) which was accompanied by an increase in guanosine 3',5'-cyclic monophosphate (cGMP) but no decrease in cell viability (trypan blue), glucose oxidation or adenosine 3',5'-cyclic monophosphate (cAMP) content. Oxyhaemoglobin (37 microM), which scavenges NO, significantly reduced the inhibitory effect of SNAP (1 mM). Prior exposure of intact cells to SNAP also reduced aminopyrine accumulation in response to ATP in permeabilised cells, an effect prevented by Rp-8-bromoguanosine 3',5'-monophosphorothioate, which inhibits activation of cGMP-dependent protein kinase, but not by the Sp-isomer. NO thus inhibits secretory activity in rat parietal cells by a specific interaction that may involve cGMP.
在大鼠离体壁细胞中，弱碱氨基比林的蓄积被用作酸分泌活性的指标。一氧化氮（NO）供体S-亚硝基-N-乙酰青霉胺（SNAP）引起氨基比林蓄积的剂量依赖性抑制（半数有效浓度为247微摩尔），同时伴有鸟苷3',5'-环磷酸（cGMP）增加，但细胞活力（台盼蓝）、葡萄糖氧化或腺苷3',5'-环磷酸（cAMP）含量无降低。可清除NO的氧合血红蛋白（37微摩尔）显著降低了SNAP（1毫摩尔）的抑制作用。完整细胞预先暴露于SNAP也会降低通透细胞中对ATP产生反应的氨基比林蓄积，这种作用可被抑制cGMP依赖性蛋白激酶激活的Rp-8-溴鸟苷3',5'-单磷酸硫代物阻止，但不能被Sp-异构体阻止。因此，NO通过一种可能涉及cGMP的特异性相互作用抑制大鼠壁细胞的分泌活性。
