Inhibition of spontaneous acetylcholine secretion by 2-chloroadenosine as revealed by a protein kinase inhibitor at the mouse neuromuscular junction.
Inhibition of spontaneous acetylcholine secretion by 2-chloroadenosine as revealed by a protein kinase inhibitor at the mouse neuromuscular junction.
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小鼠神经肌肉接头处的蛋白激酶抑制剂揭示了 2-氯腺苷对自发乙酰胆碱分泌的抑制作用。
DOI：
10.1038/sj.bjp.0704653
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发表时间：
2002
影响因子：
7.3
通讯作者：
Silinsky,EugeneM
中科院分区：
文献类型：
--
作者：
Hirsh,JodyK;Silinsky,EugeneM
先前的研究报道了A1腺苷受体激动剂在小鼠运动神经末梢的效力的差异。此外，关于蛋白激酶A（PKA）在介导A1受体激动剂的抑制作用中的作用的相互矛盾的结果已经发表。因此，我们决定研究通过蛋白激酶内源性控制腺苷受体敏感性的可能性，使用多种蛋白激酶抑制剂与腺苷受体激动剂2-氯腺苷（CADO）。CADO在先前用于研究小鼠自发ACh释放的浓度（1 μM）下，在我们的实验中没有抑制自发ACh释放。 然而，较高浓度的CADO（10 μM）可显著降低自发性ACh释放。在非选择性蛋白激酶抑制剂H7（50 μM）存在下，CADO的效力增加，1 μMCADO可将自发性ACh定量释放降低至对照组的约63%。H7和选择性PKA抑制剂KT 5720（500 nM）均可阻止CPT环AMP（250 μM）产生的ACh释放增加，表明这些激酶抑制剂可阻断PKA。 然而，与H7相反，KT 5720未显示1 μMCADO的抑制作用。 许多其他非选择性PKA抑制剂也未能增加CADO的效力。结果表明，内源性H7敏感过程调节小鼠A1腺苷受体的敏感性，CADO的抑制作用与环AMP积累或PKA抑制无关。British Journal of Pharmacology（2002）135，1897-1902; doi：10.1038/sj.bjp.0704653
Previous studies have reported discrepancies in the potencies of A1adenosine receptor agonists at mouse motor nerve terminals. In addition, conflicting results on the role of protein kinase A (PKA) in mediating the inhibitory effects of A1receptor agonists have been published. We thus decided to investigate the possibility of endogenous control of adenosine receptor sensitivity by protein kinases, using a variety of protein kinase inhibitors in conjunction with the adenosine receptor agonist 2‐chloroadenosine (CADO).CADO, at the concentration employed previously to study spontaneous ACh release in the mouse (1 μM), did not inhibit spontaneous ACh release in our experiments. However, a higher concentration of CADO (10 μM) produced highly statistically‐significant reductions in spontaneous ACh release.In the presence of the non‐selective protein kinase inhibitor, H7 (50 μM), the potency of CADO was increased such that 1 μMCADO now reduced spontaneous quantal ACh release to approximately 63% of control.Both H7, and the selective PKA inhibitor, KT5720 (500 nM) prevented increases in ACh release produced by CPT cyclic AMP (250 μM), suggesting these kinase inhibitors were blocking PKA. In contrast to H7, however, KT5720, did not reveal an inhibitory effect of 1 μMCADO. A number of other non‐selective PKA inhibitors also failed to increase the potency of CADO.The results suggest that an endogenous H7‐sensitive process modulates the sensitivity of the mouse A1adenosine receptor and that the inhibitory effects of CADO are independent of cyclic AMP accumulation or PKA inhibition.British Journal of Pharmacology(2002)135, 1897–1902; doi:10.1038/sj.bjp.0704653