Tyrosine kinase activities in the modulation of stimulated parietal cell acid secretion.
Tyrosine kinase activities in the modulation of stimulated parietal cell acid secretion.
复制标题
酪氨酸激酶活性调节刺激的壁细胞酸分泌。
DOI：
10.1152/ajpgi.1993.264.2.g351
复制
发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Goldenring,JR
中科院分区：
文献类型：
--
作者：
Tsunoda,Y;Modlin,IM;Goldenring,JR
在离体兔壁细胞上研究了蛋白酪氨酸激酶（PTK）活性对分泌调节的影响。两类抑制剂，染料木黄酮（可溶性和膜相关的PTK活性的抑制剂）和erbstatin类似物（膜相关的PTK活性的抑制剂），对促分泌素刺激以及转化生长因子-α（TGF-α）抑制进行了测试。用10（-7）M大鼠TGF-α预处理兔壁细胞，可抑制组胺和卡巴胆碱刺激的[14 C]-氨基比林（AP）蓄积。TGF-α的抑制被完全逆转，同时预处理细胞与50 μ M染料木素或erbstatin类似物，表明受体相关的PTK活性可能参与抑制壁细胞分泌。此外，染料木黄酮，而不是厄布他汀类似物，增强组胺刺激的AP积累，EC 50从1.9到0.5 μ M的变化。类似地，染料木黄酮，而不是厄布他汀类似物，增强了对毛喉素的反应，EC 50从1.5 μ M变化到0.1 μ M。染料木黄酮对二丁酰腺苷3 '，5'-环一磷酸或卡巴胆碱刺激AP摄取没有影响。此外，染料木黄酮未能增加组胺或毛喉素刺激超过最大水平，并没有显着的影响，无论是细胞腺苷3 '，5'-环磷酸生产或细胞内Ca 2+浓度。这些结果表明，PTK蛋白磷酸酪氨酸磷酸酶系统可能参与增强组胺信号的腺苷酸环化酶激活的独立机制。
The effects of protein tyrosine kinase (PTK) activities on the modulation of secretion were investigated in isolated rabbit parietal cells. Two classes of inhibitors, genistein (an inhibitor of both soluble and membrane-associated PTK activities) and an erbstatin analogue (an inhibitor of membrane-associated PTK activities), were tested against both secretagogue stimulation as well as transforming growth factor-alpha (TGF-alpha) inhibition. Pretreatment of rabbit parietal cells with 10(-7) M rat TGF-alpha resulted in inhibition of both histamine- and carbachol-stimulated [14C]-aminopyrine (AP) accumulation. TGF-alpha inhibition was totally reversed by simultaneous pretreatment of cells with 50 microM genistein or an erbstatin analogue, indicating that a receptor-associated PTK activity is likely involved in the inhibition of parietal cell secretion. Furthermore, genistein, but not the erbstatin analogue, potentiated histamine-stimulated AP accumulation with a change in EC50 from 1.9 to 0.5 microM. Similarly, genistein, but not the erbstatin analogue, potentiated the response to forskolin with a change in EC50 from 1.5 to 0.1 microM. Genistein had no effect on stimulation of AP uptake by either dibutyryladenosine 3',5'-cyclic monophosphate or carbachol. In addition, genistein failed to increase histamine or forskolin stimulation beyond the maximal level and had no significant effect on either cellular adenosine 3',5'-cyclic monophosphate production or intracellular Ca2+ concentration. These results suggest that a PTK-protein phosphotyrosine phosphatase system may be involved in the potentiation of the histamine signal by a mechanism independent of adenylate cyclase activation.