Nandi J, Crockett J, Levine R A
Department of Medicine, State University of New York Health Science Center, Syracuse.
J Pharmacol Exp Ther. 1994 Jun;269(3):932-40.
The effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on H+ secretion were studied in frog gastric mucosa and rabbit parietal cells (PC). In frog gastric mucosa, aspirin (10(-5) M) and ibuprofen (10(-4) M), but not indomethacin, naproxen and carprofen (10(-4) M each), enhanced histamine- and dibutyryl adenosine 3',5'-cyclic monophosphate-stimulated H+ secretion by 20 to 34%. Similarly, a protein kinase C (PKC) inhibitor, 1-(5-isoquinolinesulfonyl)- 2-methyl piperazine (H7, 5 x 10(-5) M), and a calcium ionophore, A23187 (10(-6) M) augmented basal and the aforementioned secretagogue-stimulated H+ secretion by approximately 50% and 20%, respectively, but a PKC activator, phorbol ester (12-O-tetradecanoyl phorbol 13-acetate, 10(-7)-10(-6) M), had no effect. The augmentation of H+ secretion by these agents was blocked by a calcium antagonist, lanthanum chloride (5 x 10(-4) M). In rabbit PC, H7 augmented secretagogue-stimulated H+ secretion by 60 to 150%, whereas 12-O-tetradecanoyl phorbol 13-acetate (10(-7) M) inhibited carbachol- and histamine-stimulated H+ secretion, respectively, by 65% and 52% without affecting dibutyryl adenosine 3',5'-cyclic monophosphate-stimulated H+ secretion. Furthermore, NSAIDs and H7-induced augmentation of dibutyryl cyclic adenosine monophosphate-stimulated H+ secretion was prevented by 12-O-tetradecanoyl phorbol 13-acetate (10(-7)-10(-6) M) in frog gastric mucosa and rabbit PC. Unlike H7, NSAIDs had no direct inhibiting action on PC membrane or cytosolic fractions of PKC, but they inhibited Sn-1,2-diacylglycerol level in PC by 20 to 30%.(ABSTRACT TRUNCATED AT 250 WORDS)
在蛙胃黏膜和兔壁细胞（PC）中研究了非甾体抗炎药（NSAIDs）对氢离子（H⁺）分泌的影响。在蛙胃黏膜中，阿司匹林（10⁻⁵ M）和布洛芬（10⁻⁴ M）可增强组胺和二丁酰腺苷3'，5'-环磷酸单酯刺激的H⁺分泌达20%至34%，但吲哚美辛、萘普生和卡洛芬（各10⁻⁴ M）则无此作用。同样，蛋白激酶C（PKC）抑制剂1-（5-异喹啉磺酰基）-2-甲基哌嗪（H7，5×10⁻⁵ M）和钙离子载体A23187（10⁻⁶ M）分别使基础分泌以及上述促分泌剂刺激的H⁺分泌增加约50%和20%，但PKC激活剂佛波酯（12-O-十四烷酰佛波醇13-乙酸酯，10⁻⁷ - 10⁻⁶ M）则无作用。这些药物引起的H⁺分泌增加被钙拮抗剂氯化镧（5×10⁻⁴ M）阻断。在兔PC中，H7使促分泌剂刺激的H⁺分泌增加60%至150%，而12-O-十四烷酰佛波醇13-乙酸酯（10⁻⁷ M）分别抑制卡巴胆碱和组胺刺激的H⁺分泌65%和52%，但不影响二丁酰腺苷3'，5'-环磷酸单酯刺激的H⁺分泌。此外，在蛙胃黏膜和兔PC中，12-O-十四烷酰佛波醇13-乙酸酯（10⁻⁷ - 10⁻⁶ M）可阻止NSAIDs和H7引起的二丁酰环腺苷单磷酸刺激的H⁺分泌增加。与H7不同，NSAIDs对PC膜或PKC的胞质部分没有直接抑制作用，但它们可使PC中的Sn-1,2-二酰甘油水平降低20%至30%。（摘要截短于250字）
