Sensitization of the contractile system of canine colonic smooth muscle by agonists and phorbol ester.
Sensitization of the contractile system of canine colonic smooth muscle by agonists and phorbol ester.
复制标题
激动剂和佛波酯对犬结肠平滑肌收缩系统的敏化。
DOI：
10.1113/jphysiol.1994.sp020473
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Gerthoffer,WT
中科院分区：
文献类型：
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作者：
Sato,K;Leposavic,R;Publicover,NG;Sanders,KM;Gerthoffer,WT
1. 在狗的结肠环形平滑肌中研究了兴奋性激动剂乙酰胆碱 (ACh)、乙酰胆碱、组胺和神经激肽 A (NKA) 组合对收缩系统的敏感性，NKA (1 nM) 增强了对 1 microMACh 的收缩反应，但没有增加 fura-2 荧光比 (R340/380)。 0.1 µM 4-佛波醇 12,13-二丁酸酯 (PDBu) 显着增强了对低浓度乙酰甲胆碱或组胺的收缩反应，表明蛋白激酶 C 的激活可以在激动剂阈值浓度下增强收缩。 2. 收缩系统对 Ca2+ 的敏感性的变化在一系列激动剂浓度下得到证实。 KCl、ACh、组胺和 NKA 均会导致阶段性收缩幅度和 R340/380 浓度依赖性增加。然而，ACh、组胺和 NKA 各自在浓度低于诱导最大力所需的浓度时诱导 R340/380 的最大增加。 3. 在去极化肌肉中，NKA (50 nM) 和 PDBu (1 microM) 各自增加强直收缩的幅度，而 R340/380 和肌球蛋白轻链磷酸化没有变化或减少。在α-毒素渗透纤维中，0.1 microM PDBu 和 1 microM NKA 将 Ca(2+) 力响应向左移动。 100 µM GTP-gamma-S 或 1 µM NKA 加 10 µM GTP 也可增强 Ca(2+) 诱导的收缩。 NKA 和 GTP 的收缩增强作用被 10 microM GDP-β-S 拮抗。 4. 结果表明，通过 G 蛋白发挥作用的内源性激动剂部分通过激活蛋白激酶 C 使结肠平滑肌的收缩元件敏感。在某些情况下，敏化可能继发于肌球蛋白磷酸化 (ACh) 增加，但在其他情况下，它似乎与肌球蛋白轻链磷酸化（NKA 和 PDBu）增加无关。因此，除了肌球蛋白磷酸化之外，调节机制也有助于收缩系统对 Ca2+ 的明显敏感性。
1. Sensitization of the contractile system in response to combinations of excitatory agonists acetylcholine (ACh), methacholine, histamine and neurokinin A (NKA) was investigated in colonic circular smooth muscle of dog, NKA (1 nM) potentiated the contractile response to 1 microM ACh, but did not increase the fura‐2 fluorescence ratio (R340/380). Contraction in response to low concentrations of either methacholine or histamine was potentiated significantly by 0.1 microM 4‐phorbol 12,13‐dibutyrate (PDBu), suggesting that activation of protein kinase C can potentiate contraction at threshold concentrations of agonists. 2. Variability in the sensitivity of the contractile system to Ca2+ was demonstrated over a range of agonist concentrations. KCl, ACh, histamine and NKA each produced a concentration‐dependent increase in the amplitude of phasic contractions and R340/380. However, ACh, histamine and NKA each induced maximal increases in R340/380 at concentrations less than that needed to induce maximum force. 3. In depolarized muscles, NKA (50 nM) and PDBu (1 microM) each increased the magnitude of tonic contraction with no change or a decrease in both R340/380 and myosin light chain phosphorylation. In alpha‐toxin‐permeabilized fibres, 0.1 microM PDBu and 1 microM NKA shifted the Ca(2+)‐force response to the left. Ca(2+)‐induced contractions were also potentiated by 100 microM GTP‐gamma‐S or 1 microM NKA plus 10 microM GTP. Potentiation of contraction by NKA and GTP was antagonized by 10 microM GDP‐beta‐S. 4. The results suggest that endogenous agonists acting via G‐proteins sensitize the contractile element of colonic smooth muscle in part by activation of protein kinase C. In some cases, sensitization may be secondary to increased myosin phosphorylation (ACh), but in other cases it appears to be independent of increased myosin light chain phosphorylation (NKA and PDBu). Therefore regulatory mechanisms in addition to myosin phosphorylation contribute to the apparent sensitization of the contractile system to Ca2+.