L-365,260 通过与蛋白激酶 A 途径相互作用来抑制体外酸分泌。
L-365,260 inhibits in vitro acid secretion by interacting with a PKA pathway.
作者信息
Oiry C, Pannequin J, Cormier A, Galleyrand J C, Martinez J
机构信息
Laboratoire des Amino Acides, Peptides et Protéines, UMR CNRS 5810, Faculté de Pharmacie, Montpellier, France.
出版信息
Br J Pharmacol. 1999 May;127(1):259-67. doi: 10.1038/sj.bjp.0702505.
The aim of this study was to analyse the antisecretory mechanism of L-365,260 in vitro in isolated rabbit gastric glands. We showed that compound L-365,260, described as a non-peptide specific competitive CCK-B receptor antagonist, was able to dose-dependently inhibit [14C]-aminopyrine accumulation induced by histamine (10(-4) M), carbachol (5x10(-5) M), 3-isobutyl-1-methyl-xanthine (IBMX) (5x10(-6) M) and forskolin (5x10(-7) M) with similar IC50 values respectively of 1.1+/-0.6x10(-7) M, 1.9+/-1.2x10(-7) M, 4.2+/-2.0x10(-7) M and 4.0+/-2.8x10(-7) M. We showed that L-365,260 acted beyond receptor activation and production of intracellular second messengers and that it had no action on the H+/K+ -ATPase. We found that L-365,260 inhibited cyclic AMP-induced [14C]-aminopyrine accumulation in digitonin-permeabilized rabbit gastric glands, suggesting that this compound acted, at least in part, as an inhibitor of the cyclic AMP-dependent protein kinase (PKA) pathway.
本研究的目的是在体外分离的兔胃腺中分析L-365,260的抗分泌机制。我们发现，化合物L-365,260被描述为一种非肽类特异性CCK-B受体拮抗剂，能够剂量依赖性地抑制由组胺（10^(-4) M）、卡巴胆碱（5×10^(-5) M）、3-异丁基-1-甲基黄嘌呤（IBMX）（5×10^(-6) M）和福斯可林（5×10^(-7) M）诱导的[14C]-氨基比林蓄积，其IC50值分别相似，为1.1±0.6×10^(-7) M、1.9±1.2×10^(-7) M、4.2±2.0×10^(-7) M和4.0±2.8×10^(-7) M。我们发现L-365,260的作用超出了受体激活和细胞内第二信使的产生，并且它对H+/K+-ATP酶没有作用。我们发现L-365,260抑制了洋地黄皂苷通透的兔胃腺中环磷酸腺苷（cAMP）诱导的[14C]-氨基比林蓄积，这表明该化合物至少部分地作为环磷酸腺苷依赖性蛋白激酶（PKA）途径的抑制剂发挥作用。
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