Inhibition of vascular KATP channels by U‐37883A: a comparison with cardiac and skeletal muscle
Inhibition of vascular KATP channels by U‐37883A: a comparison with cardiac and skeletal muscle
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U-37883A 对血管 KATP 通道的抑制：与心肌和骨骼肌的比较
DOI：
10.1038/sj.bjp.0702868
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发表时间：
1999
影响因子：
7.3
通讯作者：
J. Quayle
中科院分区：
文献类型：
--
作者：
G. Wellman;R. Barrett;H. Köppel;D. Everitt;J. Quayle
本研究的目的是研究三磷酸腺苷敏感钾通道抑制剂U-37883A(4‐morpholinecarboximidine‐N‐1‐adamantyl‐N′‐1‐cyclohexyl).的选择性用酶法分离的大鼠肠系膜动脉、心室和骨骼肌(指短屈肌)的单个肌细胞记录到通过KATP通道的膜电流。用0.1 mM ATP和0.1 mM ADP进行细胞透析，或应用人工合成的钾通道开放剂(左旋克罗卡林或吡那地尔)，均可诱发KATP电流。U-37883A抑制大鼠肠系膜动脉平滑肌细胞的KATP电流。U-37883A可半抑制10 μM左旋克罗卡林诱发的电流，其作用可被U-37883A逆转。左旋克罗卡林对大鼠肠系膜血管的松弛作用可被U-37883A所逆转。1、U-37883A(半数抑制浓度，1.1 μM)可抑制左旋克罗卡林引起的心肌细胞松弛。在大鼠肠系膜动脉、骨骼肌和心室肌的单个细胞上，也观察了10 0 μM吡那地尔激活的KATP电流。10 μM U-37883A可显著抑制血管细胞的KATP电流，但对骨骼肌细胞和心肌细胞的作用不明显。较高浓度的U-37883A(100 μM)可使骨骼肌和心肌的KATP电流略有下降。磺脲类钾通道拮抗剂格列本脲(10 μM)可阻断所有肌肉类型的电流。同时观察U-37883A对血管内向整流电流(KIR)和电压依赖性钾电流(KV)的影响。10 μM U-37883A对上述电流影响不大，但在较高浓度(10 0 μM)时有一定的抑制作用。我们得出结论：U-37883A抑制动脉平滑肌的KATP通道比抑制心肌和骨骼肌的KATP通道更有效。此外，该化合物对平滑肌细胞上KV和KIR通道上的KATP通道具有选择性。
The aim of this study was to investigate the selectivity of the ATP‐sensitive potassium (KATP) channel inhibitor U‐37883A (4‐morpholinecarboximidine‐N‐1‐adamantyl‐N′‐1‐cyclohexyl). Membrane currents through KATP channels were recorded in single muscle cells enzymatically isolated from rat mesenteric artery, cardiac ventricle and skeletal muscle (flexor digitorum brevis). KATP currents were induced either by cell dialysis with 0.1 mM ATP and 0.1 mM ADP, or by application of synthetic potassium channel openers (levcromakalim or pinacidil). U‐37883A inhibited KATP currents in smooth muscle cells from rat mesenteric artery. Half inhibition of 10 μM levcromakalim‐induced currents occurred at a concentration of 3.5 μM. Relaxations of rat mesenteric vessels caused by levcromakalim were reversed by U‐37883A. 1 μM levcromakalim‐induced relaxations were inhibited at a similar concentration of U‐37883A (half inhibition, 1.1 μM) to levcromakalim‐induced KATP currents. KATP currents activated by 100 μM pinacidil were also studied in single myocytes from rat mesenteric artery, skeletal muscle and cardiac ventricle. 10 μM U‐37883A substantially inhibited KATP currents in vascular cells, but had little effect in skeletal or cardiac myocytes. Higher concentrations of U‐37883A (100 μM) caused a modest decrease in KATP currents in skeletal and cardiac muscle. The sulphonylurea KATP channel antagonist glibenclamide (10 μM) abolished currents in all muscle types. The effect of U‐37883A on vascular inward rectifier (KIR) and voltage‐dependent potassium (KV) currents was also examined. While 10 μM U‐37883A had little effect on these currents, some inhibition was apparent at higher concentrations (100 μM) of the compound. We conclude that U‐37883A inhibits KATP channels in arterial smooth muscle more effectively than in cardiac and skeletal muscle. Furthermore, this compound is selective for KATP channels over KV and KIR channels in smooth muscle cells.
DOI：
10.1152/ajpheart.1996.271.2.h696
发表时间：
1996-08-01
影响因子：
4.8
作者：
Robertson, BE;Bonev, AD;Nelson, MT
通讯作者：
Nelson, MT