ns19504  (Alomone Labs)

Journal: Scientific Reports

Article Title: Pharmacological activation of BK channels protects against LPS-induced pneumonia

doi: 10.1038/s41598-025-08902-6

Figure Lengend Snippet: Pharmacological BK channel activation protects mice against LPS-induced pneumonia. LPS infection ( i.t. , 10 mg/kg) increased BALF total cell ( a , k ) and neutrophil counts ( b , l ), and BALF CCL-2 ( c , n ), MIP-1α ( o ) and CXCL-10 ( p ) concentrations, lung injury scores ( d , e ), and cytosolic ROS production by BALF cells ( f , m ). Two doses of the BK activator NS1619 or NS19504 ( i.t. , 0.66 mg/kg), given at 0 and 24 h improved all measured markers of acute lung injury. In contrast, mitochondrial ROS production ( g ), BALF total protein levels ( h , q ), quasi-static lung compliance ( i , r ), and body weight loss ( j , s ) were not affected by NS1619 treatment. Control mice received equimolar drug vehicle injections. n = 3–10 mice per group; individual experimental data points are depicted within each bar; bars depict mean ± SEM; *p < 0.05; IF—intensity of fluorescence; A.U.—arbitrary units; scale bar: 650 µm.

Article Snippet: Separate groups also received i.t. injections of the BK channel activator NS1619 (0.66 mg/kg in 50 μl in sterile PBS; Millipore, Burlington, MA) or NS19504 (1.33 mg/kg in 50 μl in sterile PBS; Alomone labs, Israel), the BK channel blocker Paxilline (1.33 mg/kg in 50 μl in sterile PBS; Alomone labs, Israel), or equimolar vehicle controls, at times 0 and 24 h. We then quantified the degree of lung injury at 48 h. This model resulted in a moderate degree of lung injury with potential for recovery (< 3% mortality), representing a clinically relevant infection.

Techniques: Activation Assay, Infection, Control, Fluorescence

Journal: Scientific Reports

Article Title: Pharmacological activation of BK channels protects against LPS-induced pneumonia

doi: 10.1038/s41598-025-08902-6

Figure Lengend Snippet: Pharmacological activation of BK channels with NS1619 (30 μM) or NS19504 (30 μM) administered at 0 h protects primary human alveolar epithelial cells (HPAEpiC against LPS (2 μg/ml) -induced ROS production ( a ). In contrast, primary human pulmonary artery endothelial cells (HPAEC) showed no ROS response to LPS treatment ( b ). Control cells were treated with an equimolar drug vehicle. n = 3–7 separate experimental repeats; individual experimental data points are shown within each bar; bars represent mean ± SEM; * p < 0.05; IF – intensity of fluorescence; A.U.—arbitrary units.

Article Snippet: Separate groups also received i.t. injections of the BK channel activator NS1619 (0.66 mg/kg in 50 μl in sterile PBS; Millipore, Burlington, MA) or NS19504 (1.33 mg/kg in 50 μl in sterile PBS; Alomone labs, Israel), the BK channel blocker Paxilline (1.33 mg/kg in 50 μl in sterile PBS; Alomone labs, Israel), or equimolar vehicle controls, at times 0 and 24 h. We then quantified the degree of lung injury at 48 h. This model resulted in a moderate degree of lung injury with potential for recovery (< 3% mortality), representing a clinically relevant infection.

Techniques: Activation Assay, Control, Fluorescence

Journal: Scientific Reports

Article Title: Pharmacological activation of BK channels protects against LPS-induced pneumonia

doi: 10.1038/s41598-025-08902-6

Figure Lengend Snippet: ( a ) BK channel-mediated network analysis predicts cytokine and ROS clusters connected through hydrogen peroxide (H 2 O 2 ) in an in silico model. A protein-drug interaction network was constructed using the STITCH database to investigate the relationships between BK channels, oxidative stress, and inflammatory molecules in an LPS-induced pneumonia model. The network includes BK channels (KCNMA1), BK channel activators (NS1619/NS19504), neutrophil/macrophage chemoattractants (CCL-2, MIP-1α, CXCL-10), and oxidative stress enzymes (SOD1, catalase). The network analysis identified two distinct clusters: a ROS cluster (including SOD2, zinc, and copper) and a cytokine cluster (including CCL-4, CXCR-2, CCR-2, CCL-5, and CXCL-9). These clusters are interconnected by H 2 O 2 , linking ROS production and cytokine release to BK channels in LPS-induced pneumonia. Dashed lines represent connections identified in this study; red nodes indicate query proteins obtained in this study, while gray nodes represent the most likely downstream interaction partners with a high confidence level (0.95 on a 0–1 scale). ( b ) Schematic diagram of the proposed mechanism underlying BK channel activation-mediated protection against LPS-induced oxidative stress.

Article Snippet: Separate groups also received i.t. injections of the BK channel activator NS1619 (0.66 mg/kg in 50 μl in sterile PBS; Millipore, Burlington, MA) or NS19504 (1.33 mg/kg in 50 μl in sterile PBS; Alomone labs, Israel), the BK channel blocker Paxilline (1.33 mg/kg in 50 μl in sterile PBS; Alomone labs, Israel), or equimolar vehicle controls, at times 0 and 24 h. We then quantified the degree of lung injury at 48 h. This model resulted in a moderate degree of lung injury with potential for recovery (< 3% mortality), representing a clinically relevant infection.

Techniques: In Silico, Construct, Activation Assay