Tyrosine kinase involvement in apamin‐sensitive inhibitory responses of rat distal colon

Tyrosine kinase involvement in apamin‐sensitive inhibitory responses of rat distal colon
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酪氨酸激酶参与大鼠远端结肠的 apamin 敏感抑制反应

DOI:
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发表时间:
1999
期刊:
Journal of Physiology
影响因子:
--
通讯作者:
T. Takewaki
T. Takewaki
中科院分区:
--
文献类型:
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作者:
T. Takeuchi;M. Kishi;N. Hirayama;M. Yamaji;T. Ishii;H. Nishio;F. Hata;T. Takewaki

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1 有人提出,垂体腺苷酸环化酶激活肽 (PACAP) 可能参与大鼠远端结肠纵肌的非肾上腺素能、非胆碱能 (NANC) 抑制反应。在这项研究中,我们研究了 PACAP 诱导该肌肉松弛的细胞内机制。 2 PACAP 诱导 apamin 敏感的纵向肌肉松弛。 10 μm 的酪氨酸激酶抑制剂金雀异黄酮和 30 μm 的酪氨酸激酶抑制剂 25,但 30 μm 的环 AMP 依赖性蛋白激酶抑制剂 Rp-8-溴腺苷-3',5'-环单磷酸硫代酯则不能显着抑制 PACAP 诱导的松弛,分别达到对照值的 60% 和 25%。 PACAP 不会增加肌肉的环磷酸腺苷含量。 3 10 μm 的 Tyrphostin 25 显着抑制电场刺激 (EFS) 诱导的纵向肌肉松弛,达到对照值的 50%。 1 μm 的 Apamin 是一种小电导 Ca2+ 激活的 K+ 通道的拮抗剂,也抑制松弛,达到对照值的 42%。酪氨酸磷酸酶 25 和 apamin 的抑制作用不是相加的(对照值的 44%)。 4 PACAP 诱导肌肉细胞膜对 apamin 敏感、缓慢超极化。 3 μm 的 Tyrphostin 25 抑制 PACAP 诱导的超极化。 10 μm 的酪氨酸磷酸酶 25 和 10 μm 的染料木黄酮抑制 EFS 单脉冲诱导的 apamin 敏感的抑制性连接电位。 5 PACAP 诱导的纵向肌肉松弛伴随着细胞内 Ca2+ 水平 ([Ca2+]i) 的降低。 10 μm 的 Tyrphostin 25 和 1 μm 的 apamin 消除了这些 PACAP 诱导的反应。 6 这些发现表明,酪氨酸激酶的激活参与 PACAP 诱导的大鼠远端结肠纵向肌肉的松弛,即 apamin 敏感 K+ 通道激活的“上游”。
1 It has been suggested that pituitary adenylate cyclase activating peptide (PACAP) may be involved in the non‐adrenergic, non‐cholinergic (NANC) inhibitory response of longitudinal muscle of rat distal colon. In this study, we have investigated the intracellular mechanism of PACAP‐induced relaxation in this muscle. 2 PACAP induced an apamin‐sensitive relaxation of the longitudinal muscle. The tyrosine kinase inhibitors genistein at 10 μm and tyrphostin 25 at 30 μm, but not the cyclic AMP‐dependent protein kinase inhibitor Rp‐8‐bromoadenosine‐3′,5′‐cyclic monophosphorothioate at 30 μm significantly inhibited the PACAP‐induced relaxation to 60% and 25% of control values, respectively. PACAP did not increase the cyclic AMP content of the muscle. 3 Tyrphostin 25 at 10 μm significantly inhibited the relaxation of longitudinal muscle induced by electrical field stimulation (EFS), to 50% of control values. Apamin at 1 μm, an antagonist of small conductance Ca2+‐activated K+ channels, also inhibited the relaxation, to 42% of control values. The inhibitory effects of tyrphostin 25 and apamin were not additive (44% of control values). 4 PACAP induced an apamin‐sensitive, slow hyperpolarization of the cell membrane of the muscle. Tyrphostin 25 at 3 μm inhibited this PACAP‐induced hyperpolarization. Tyrphostin 25 at 10 μm and genistein at 10 μm inhibited the apamin‐sensitive inhibitory junction potentials induced by a single pulse of EFS. 5 The PACAP‐induced relaxation of longitudinal muscle occurred with a concomitant decrease in intracellular Ca2+ levels ([Ca2+]i). Tyrphostin 25 at 10 μm and apamin at 1 μm abolished these PACAP‐induced responses. 6 From these findings it is suggested that the activation of tyrosine kinase is involved in PACAP‐induced relaxation of longitudinal muscle from rat distal colon, ‘upstream of’ the activation of apamin‐sensitive K+ channels.
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