Potassium channel activator bl-1249 inhibits the c-fos response to parathyroid hormone in osteoblastic cells in a dose-dependent manner

Bone ◽  
2009 ◽  
Vol 44 ◽  
pp. S304
Author(s):  
A.W. Gallagher ◽  
J.M. Quayle ◽  
J.A. Gallagher⁎
2006 ◽  
Vol 95 (6) ◽  
pp. 1039-1047 ◽  
Author(s):  
Wen-Fang Chen ◽  
Man-Sau Wong

Genistein and parathyroid hormone (PTH) are anabolic agents that stimulate bone formation through their direct actions in osteoblastic cells. In the present study, we aimed to determinewhether genistein modulates the actions of PTH in human osteoblastic SaOS-2 cells in an oestrogen-depleted condition. The present results showed that genistein (10−8to 10−6m) induced alkaline phosphatase (ALP) activity and osteoprotegrin (OPG) expression in SaOS-2 cells in a dose-dependent manner. These effects could be completely abolished by co-treatment with oestrogen antagonist ICI 182780 (7α-[9-[(4,4,5,5,5-pentafluoropentyl)sulfonyl]nonyl]-estra-1,3,5(10)-triene-3,17β-diol). Genistein (at 1μm) could stimulate the mRNA expression of receptor activator of NF-κB ligand (RANKL). As OPG and RANKL are known to modulate osteoclastogenesis, the ability of genistein to modulate OPG and RANKL expression in SaOS-2 cells suggested that it might modulate osteoclastogenesis through its direct actions on osteoblastic cells. PTH (at 10nm) stimulated ALP activity, induced RANKL mRNA expression and suppressed OPG mRNA expression in SaOS-2 cells, confirming its bi-directional effects on osteoblastic cells. Pre-treatment of SaOS-2 cells with genistein andoestrogen not only enhanced PTH-induced ALP activity, but also attenuated PTH up regulation ofRANKL mRNA expression and PTH down regulation of OPG mRNA expression. Taken together, the present study provides the first evidence that genistein could modulate the actions of PTH in human osteoblastic SaOS-2 cells in an oestrogen-depleted condition.


2012 ◽  
Vol 2012 ◽  
pp. 1-4 ◽  
Author(s):  
Hung-Hao Lee ◽  
Po-Chao Hsu ◽  
Tsung-Hsien Lin ◽  
Wen-Ter Lai ◽  
Sheng-Hsiung Sheu

Nicorandil is an antianginal agent with nitrate-like and ATP-sensitive potassium channel activator properties. After activation of potassium channels, potassium ions are expelled out of the cells, which lead to membrane hyperpolarization, closure of voltage-gated calcium channels, and finally vasodilation. We present a uremic case suffering from repeated junctional bradycardia, especially before hemodialysis. After detailed evaluation, nicorandil was suspected to be the cause of hyperkalemia which induced bradycardia. This case reminds us that physicians should be aware of this potential complication in patients receiving ATP-sensitive potassium channel activator.


Physiology ◽  
1990 ◽  
Vol 5 (5) ◽  
pp. 212-215
Author(s):  
H Suzuki ◽  
G Chen

Acetylcholine hyperpolarizes the membrane of vascular smooth muscles by increasing potassium permeability, the response being mediated by an endothelium-derived hyperpolarizing factor (EDHF). The membrane hyperpolarization produced by EDHF is therefore one of the components contributing to endothelium-dependent relaxation of vascular smooth muscles.


1989 ◽  
Vol 258 (3) ◽  
pp. 889-894 ◽  
Author(s):  
T Mine ◽  
I Kojima ◽  
E Ogata

The synthetic 1-34 fragment of human parathyroid hormone (1-34hPTH) stimulated glucose production in isolated rat hepatocytes. The effect of 1-34hPTH was dose-dependent and 10(10) M-1-34 hPTH elicited the maximum glucose output, which was approx. 80% of that by glucagon. Although 1-34hPTH induced a small increase in cyclic AMP production at concentrations higher than 10(-9) M, 10(-10) M-1-34hPTH induced the maximum glucose output without significant elevation of cyclic AMP. This is in contrast to the action of forskolin, which increased glucose output to the same extent as 10(-10) M-1-34hPTH by causing a 2-fold elevation of cyclic AMP. In addition to increasing cyclic AMP, 1-34hPTH caused an increase in cytoplasmic free calcium concentration ([Ca2+]c). When the effect of 1-34hPTH on [Ca2+]c was studied in aequorin-loaded cells, low concentrations of 1-34hPTH increased [Ca2+]c: the 1-34hPTH effect on [Ca2+]c was detected at as low as 10(-12) M and increased in a dose-dependent manner. 1-34hPTH increased [Ca2+]c even in the presence of 1 microM extracellular calcium, suggesting that PTH mobilizes calcium from an intracellular pool. In line with these observations, 1-34hPTH increased the production of inositol trisphosphate. These results suggest that: (1) PTH activates both cyclic AMP and calcium messenger systems and (2) PTH stimulates glycogenolysis mainly via the calcium messenger system.


1994 ◽  
Vol 2 (2) ◽  
pp. 300-310
Author(s):  
Bruce P. Damiano ◽  
Edward C. Giardino ◽  
Barbara J. Haertlein ◽  
Gary L. Stump ◽  
John A. Mitchell ◽  
...  

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