Journal
BRITISH JOURNAL OF PHARMACOLOGY
Volume 168, Issue 5, Pages 1230-1239Publisher
WILEY
DOI: 10.1111/bph.12000
Keywords
sympathetic nervous system; osteoblast; potassium channels; cell proliferation; heterotrimeric G-protein
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Funding
- Ministry of Education, Culture, Sports, Science and Technology of Japan [21890276]
- Strategic Research AGU-Platform Formation
- Grants-in-Aid for Scientific Research [21890276] Funding Source: KAKEN
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Background and Purpose Recent studies demonstrated that the sympathetic nervous system regulates bone metabolism via 2-adrenoceptors. Although -adrenoceptors are also expressed in osteogenic cells, their functions in bone metabolism have been less studied. We previously demonstrated that noradrenaline suppressed potassium currents via 1B-adrenoceptors in the human osteoblast SaM-1 cell line. The aim of this study was to investigate the signal transduction pathway and the physiological role of noradrenaline in human osteoblasts in more detail. Experimental Approach To investigate signal transduction through 1B-adrenoceptors, we used whole-cell patch clamp recording and Ca fluorescence imaging. Potassium channels regulate membrane potential and cell proliferation activity in non-excitable cells, so we evaluated cell proliferation activity by BrdU incorporation and WST assay. Key Results In SaM-1 cells, bath-applied noradrenaline elevated intracellular Ca2+ concentration and this effect was abolished by both chloroethylclonidine, an 1B-adrenoceptor antagonist, and U73122, a PLC inhibitor. However, the inhibitory effect of noradrenaline on whole-cell current was unaffected by U73122. In contrast, in cells pretreated with either Pertussis toxin, a Gi/o-protein-coupled receptor inhibitor, or gallein, a G-protein inhibitor, the inhibitory effect of noradrenaline on whole-cell current was significantly suppressed. Noradrenaline-induced enhancement of cell proliferation was inhibited by CsCl, a non-selective potassium channel blocker, gallein and H89, a PKA inhibitor, but not by U73122. Conclusions and Implications Noradrenaline facilitated cell proliferation by regulation of potassium currents in human osteoblasts via Gi/o-protein-coupled 1B-adrenoceptors, not via coupling to Gq-proteins.
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