Evidence for activation of BKCa channels by a known inhibitor of focal adhesion kinase, PF573228

So, Edmund Cheung; Wu, King Chuen; Liang, Chia Hua; Chen, Jen Yin; Wu, Sheng Nan

doi:10.1016/j.lfs.2011.08.013

Cited by 19 publications

(15 citation statements)

References 35 publications

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“…Consistent with the results reported previously for BK Ca channels (Huang et al, 2012;So et al, 2011), both PF573228 and BMS191011 were effective at increasing I K (Ca) in U373 cells, while ketamine and verruculogen could clearly diminish it.…”

Section: Effects Of Trip On Kinetic Behavior Of Kir Channels Measuredsupporting

confidence: 91%

High effectiveness of triptolide, an active diterpenoid triepoxide, in suppressing Kir-channel currents from human glioma cells

Chen

et al. 2014

European Journal of Pharmacology

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Section: Effects Of Trip On Kinetic Behavior Of Kir Channels Measuredsupporting

confidence: 91%

High effectiveness of triptolide, an active diterpenoid triepoxide, in suppressing Kir-channel currents from human glioma cells

Chen

et al. 2014

European Journal of Pharmacology

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“…Because these conditions may differ considerably from ex vivo tissues, we used higher concentrations. Indeed, even in cultured or isolated cells, concentrations exceeding the K i values are required, ranging between 30 nM and 10 M for PF-573228 and between 10 and 100 M for Y-11 (7,12,16,36,37). We observed that both inhibitors reduced the phosphorylation of FAK at its autophosphorylation sites, Tyr 397 and Tyr 925 , in phenylephrine-challenged prostate strips.…”

Section: Discussionmentioning

confidence: 76%

Inhibition of smooth muscle force generation by focal adhesion kinase inhibitors in the hyperplastic human prostate

Kunit

Gratzke

Schreiber

et al. 2014

American Journal of Physiology-Renal Physiology

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Smooth muscle contraction may be critical for lower urinary tract symptoms (LUTS) in patients with benign prostate hyperplasia and requires stable anchorage of the cytoskeleton to the cell membrane. These connections are regulated by focal adhesion kinase (FAK). Here, we addressed the involvement of FAK in the regulation of smooth muscle contraction in hyperplastic human prostate tissues. Prostate tissues were obtained from radical prostatectomy. Expression of FAK and focal adhesion proteins was assessed by Western blot analysis and immunohistochemical stainings. Effects of the FAK inhibitors PF-573228 and Y-11 on contraction of prostate strips were examined in the organ bath. Expression of FAK and focal adhesion proteins (integrin-5α, paxilin, and c-Src) was detected by Western blot analysis in prostate samples. By double immunofluorescence staining with calponin and pan-cytokeratin, expression of FAK was observed in stromal and epithelial cells. Immunoreactivity for FAK colocalized with integrin-5α, paxilin, talin, and c-Src. Stimulation of prostate tissues with the α1-adrenergic agonist phenylephrine increased the phosphorylation state of FAK at Tyr³⁹⁷ and Tyr⁹²⁵ with different kinetics, which was blocked by the α1-adrenoceptor antagonist tamsulosin. Norepinephrine and phenylephrine induced concentration-dependent contractions of prostate strips. Both FAK inhibitors PF-573228 and Y-11 significantly inhibited norepinephrine- and phenylephrine-induced contractions. Finally, PF-573228 and Y-11 inhibited contractions induced by electric field stimulation, which was significant at the highest frequency. In conclusion, α1-adrenergic smooth muscle contraction or its regulation involves FAK in the human prostate. Consequently, FAK may be involved in the pathophysiology of LUTS and in current or future LUTS therapies.

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“…8). After to activate BK Ca channels, while paxilline was effective at inhibiting them [31]. Hence, by comparison, BK Ca channels inherent in these cells is not sensitive to inhibition by OXAL.…”

Section: Effects Of Oxal On Single-channel Conductance Of Ik Ca Channelsmentioning

confidence: 86%

“…With the aid of Chem3D and ChemDraw programs embedded in ChemBio3D Ultra version 14 (PerkinElmer; Waltham, MA), the different parameters for OXAL/Na, OXAL/Ca, cisplatin/Na and cisplatin/ Ca complexes including torsion energy, 1,4-Van der Waals force, and bend, stretch and stretch-bend energies, were calculated and compared [31].…”

Section: Calculation Of Energies Among Different Complexesmentioning

confidence: 99%

The Inhibition by Oxaliplatin, a Platinum-Based Anti-Neoplastic Agent, of the Activity of Intermediate-Conductance Ca2+-Activated K+ Channels in Human Glioma Cells

Huang

2015

Cell Physiol Biochem

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Oxaliplatin (OXAL) is a third-generation organoplatinum which is effective against advanced cancer cells including glioma cells. How this agent and other related compounds interacts with ion channels in glioma cells is poorly understood. OXAL (100 µM) suppressed the amplitude of whole-cell K⁺ currents (I_K); and, either DCEBIO or ionomycin significantly reversed OXAL-mediated inhibition of I_K in human 13-06-MG glioma cells. In OXAL-treated cells, TRAM-34 did not suppress I_K amplitude in these cells. The intermediate-conductance Ca²⁺-activated K⁺ (IK_Ca) channels subject to activation by DCEBIO and to inhibition by TRAM-34 or clotrimazole were functionally expressed in these cells. Unlike cisplatin, OXAL decreased the probability of IK_Ca-channel openings in a concentration-dependent manner with an IC₅₀ value of 67 µM. No significant change in single-channel conductance of IK_Ca channels in the presence of OXAL was demonstrated. Neither large-conductance Ca²⁺-activated K⁺ channels nor inwardly rectifying K⁺ currents in these cells were affected in the presence of OXAL. OXAL also suppressed the proliferation and migration of 13-06-MG cells in a concentration- and time-dependent manner. OXAL reduced IK_Ca-channel activity in LoVo colorectal cancer cells. Taken together, the inhibition by OXAL of IK_Ca channels would conceivably be an important mechanism through which it acts on the functional activities of glioma cells occurring in vivo.

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Evidence for activation of BKCa channels by a known inhibitor of focal adhesion kinase, PF573228

Cited by 19 publications

References 35 publications

High effectiveness of triptolide, an active diterpenoid triepoxide, in suppressing Kir-channel currents from human glioma cells

High effectiveness of triptolide, an active diterpenoid triepoxide, in suppressing Kir-channel currents from human glioma cells

Inhibition of smooth muscle force generation by focal adhesion kinase inhibitors in the hyperplastic human prostate

The Inhibition by Oxaliplatin, a Platinum-Based Anti-Neoplastic Agent, of the Activity of Intermediate-Conductance Ca2+-Activated K+ Channels in Human Glioma Cells

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