Murphy K T, Bundgaard H, Clausen T
Institute of Physiology and Biophysics, University of Aarhus, Arhus, Denmark.
Br J Pharmacol. 2006 Nov;149(6):635-46. doi: 10.1038/sj.bjp.0706896. Epub 2006 Oct 3.
In cardiac muscle, BRL 37344, a selective beta3-adrenoceptor agonist, activates the Na+, K+ -pump via NO signalling. This study investigated whether BRL 37344 also activates the Na+, K+ -pump via beta3-adrenoceptors in skeletal muscle.
Isolated rat soleus muscles were incubated between 1 and 60 min in buffer. Intracellular Na+, K+ content and Na+, K+ -pump activity were measured using flame photometry and ouabain-suppressible 86Rb+ uptake, respectively. Additional muscles were mounted on force transducers and stimulated (60 Hz for 2 s) every 10 min.
BRL 37344 (10(-8) -10(-5) M) induced a concentration- and time-dependent reduction in intracellular Na+, and increased ouabain-suppressible 86Rb+ uptake by up to 112%. BRL 37344-induced reductions in intracellular Na+ were blocked by the beta1/beta2-adrenoceptor antagonist, nadolol (10(-7) M), and the beta2-adrenoceptor antagonist, ICI 118,551 (10(-7) -10(-5) M), but not by beta3- or beta1-adrenoceptor antagonists, SR 59230A (10(-7) M) and CGP 20712A (10(-7) -10(-5) M), respectively. Another beta3-adrenoceptor agonist, CL 316,243, did not alter intracellular Na+. BRL 37344-induced reductions in intracellular Na+ were not blocked by L-NAME, an NOS inhibitor, or ODQ, a guanylyl cyclase inhibitor. The NO donors, SNP and SNAP, did not alter intracellular Na+. BRL 37344 rapidly recovered force in muscles depressed by high [K+]o, an effect that was blocked by nadolol, but not L-NAME.
In rat soleus muscle, the beta3-adrenoceptor agonist BRL 37344 stimulated the Na+, K+ -pump via beta2-adrenoceptors. A more selective beta3-adrenoceptor agonist did not affect Na+, K+ homeostasis in skeletal muscle. NO did not seem to mediate Na+, K+ -pump stimulation in skeletal muscle.
在心肌中，选择性β3肾上腺素能受体激动剂BRL 37344通过NO信号通路激活钠钾泵。本研究调查了BRL 37344是否也通过骨骼肌中的β3肾上腺素能受体激活钠钾泵。
将分离的大鼠比目鱼肌在缓冲液中孵育1至60分钟。分别使用火焰光度法和哇巴因抑制的86Rb+摄取来测量细胞内钠、钾含量和钠钾泵活性。另外的肌肉安装在力传感器上，每10分钟刺激一次（60赫兹，持续2秒）。
BRL 37344（10^(-8)-10^(-5) M）引起细胞内钠浓度和时间依赖性降低，并使哇巴因抑制的86Rb+摄取增加高达112%。BRL 37344引起的细胞内钠降低被β1/β2肾上腺素能受体拮抗剂纳多洛尔（10^(-7) M）和β2肾上腺素能受体拮抗剂ICI 118,551（10^(-7)-10^(-5) M）阻断，但未被β3或β1肾上腺素能受体拮抗剂SR 59230A（10^(-7) M）和CGP 20712A（10^(-7)-10^(-5) M）阻断。另一种β3肾上腺素能受体激动剂CL 316,243未改变细胞内钠。BRL 37344引起细胞内钠降低未被NOS抑制剂L-NAME或鸟苷酸环化酶抑制剂ODQ阻断。NO供体SNP和SNAP未改变细胞内钠。BRL 37344能迅速恢复高细胞外钾浓度抑制的肌肉的力量，该作用被纳多洛尔阻断，但未被L-NAME阻断。
在大鼠比目鱼肌中，β3肾上腺素能受体激动剂BRL 37344通过β2肾上腺素能受体刺激钠钾泵。一种更具选择性的β3肾上腺素能受体激动剂不影响骨骼肌中的钠钾稳态。NO似乎不介导骨骼肌中钠钾泵的刺激作用。
