Disease relevance of NPPB

• Furosemide and NPPB blocked the outward-rectifying lactate current and the sorbitol hemolysis with IC(50)s in the range of 0.1 and 1 microM, respectively [1].
• Replacement of intracellular Cl- by impermeant anions, as well as treatment of insulinoma cells by the Cl- channel blocker, NPPB, leads to activation of ATP-dependent K+ (KATP) channels [2].
• Therefore, arterial hypotension may be a necessary but not sufficient condition for the development of "steal" and NPPB [3].
• Control of hemorrhage during AVM surgery is one of the key issues to prevent NPPB [4].

High impact information on NPPB

• The capability to inhibit GCAC1 increases in a dose-dependent manner in the sequence: probenecid less than A-9-C less than ethacrynic acid less than niflumic acid less than IAA-94 less than NPPB [5].
• 1) In PANC-1 cells, cAMP causes parallel activation of Cl- channels and of HCO3- extrusion by DIDS-sensitive and Na+-independent Cl-/HCO3- exchange, both effects being inhibited by Cl- channel blockers NPPB and glibenclamide [6].
• Long-term (70 days) induced expression increased COL1A1 and COL1A3 mRNAs levels and collagen volume fraction and reduced levels of NPPA and NPPB [7].
• In contrast, the IC(50)s of NPPB and furosemide for the inward-rectifying current were >10 microM [1].
• GaCl was not affected by the putative Cl- channel blockers Cu2+, DIDS, DNDS, DPC, furosemide, IAA-94, MK-196, NPPB, SITS, verapamil, and glibenclamide [8].

Biological context of NPPB

• Localization of the human B-type natriuretic peptide precursor (NPPB) gene to chromosome 1p36 [9].
• Analysis of Southern blot hybridization to DNAs from various somatic cell hybrids and fluorescence in situ hybridization allowed assignment of the NPPB locus to human chromosome 1p36 [9].
• Membrane depolarization activated outward K+ and Cl- currents; quinidine was found to block the K+ current (IC50 approximately 1 microM), and NPPB reduced the Cl- current [10].
• 4. The Cl- channel blocker NPPB (5-nitro-2-(3-phenylpropylamino) benzoic acid; 50 microM) induced a 12 % increase in cell volume and a 77 % decrease in the rate of cell proliferation [11].
• Measurements of fluorescence induction kinetics and thermoluminescence suggest that the binding of NPPB to the QB binding site of PS II is similar to the herbicide DCMU (3-(3,4-dichlorophenyl)-1,1-dimethylurea) [12].

Anatomical context of NPPB

• Direct comparison of NPPB and DPC as probes of CFTR expressed in Xenopus oocytes [13].
• The Cl- channel blocker NPPB (5-nitro-2-(3-phenylpropylamino) benzoic acid) inhibited photosynthetic oxygen evolution of isolated thylakoid membranes in a pH-dependent manner with a K(i) of about 2 microM at pH 6 [12].
• The resting O2 consumption of murine peritoneal macrophages was stimulated up to 2.5-fold in the presence of NPPB, with a K0.5 of 15 microM [14].
• NPPB also mediated rheogenic proton transport across the plasma membrane of human neutrophils and macrophages in the direction dictated by the electrochemical proton gradient [14].
• When tested in a mitogenic assay, DIDS, flufenamic acid, NPPB and IAA-94 all inhibited T-cell proliferation, suggesting a physiological function in addition to the observed volume sensitivity [15].

Associations of NPPB with chemical compounds

• Chloride channel blockers (9-AC, DPC and NPPB) inhibited the cAMP-induced chloride efflux [16].
• In addition, the Cl channel blockers 5-nitro-2-(3-phenylpropylamino)benzoate (NPPB; 50 microM) and diphenylamine-2-carboxylic acid (DPC; 3 mM) reduced the cAMP-evoked currents by only approximately 10% [17].
• Addition of the Cl- channel blockers NPPB, glibenclamide, or bumetanide and experiments using Cl- free alveolar instillate solutions indicate that the accelerated AFC in this model is due to increased Cl- channel function [18].
• 4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulphonic acid (SITS, 5 x 10(-5) M) and 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB, 1 x 10(-5) M) caused an irreversible 'flickery' blockade without altering single-channel current [19].
• The RVD was inhibited by extracellular applications of the chloride channel blockers tamoxifen (30 microM; 61% inhibition), 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB, 100 microM; 60% inhibition), and ATP (10 mM; 91% inhibition) [20].

Regulatory relationships of NPPB

• These results indicate that both NPPB and DPC block CFTR by entering the pore from the cytoplasmic side and that the structural requirements for binding are not the same, although the binding regions within the pore are similar [13].
• NPPB inhibited VIP-stimulated Cl- uptake into T84 cells with an IC50 of 414 microM [21].

Other interactions of NPPB

• Release was also blocked by channel blocker NPPB and Ca(2+) chelator BAPTA, but not by cystic fibrosis transmembrane conductance regulator (CFTR) blocker glibenclamide or vesicular release inhibitor brefeldin A [22].
• Furthermore, we show that the SLC26A4 induced chloride uptake in HEK293-Phoenix cells competes with iodide, and, in addition, that the chloride uptake can be blocked by NPPB and niflumic acid, whereas DIDS is ineffective [23].
• The Cl- channel blocker NPPB (10 microM, n = 5) inhibited the EGF-mediated hyperpolarization. mRNA expression of NPR-B and NPR-Bi shows reversed patterns along the human nephron [24].
• These findings suggest that NPPB-sensitive and stilbene-insensitive Cl(-) channels other than ClC-2 play important roles in cell cycles and cell proliferation of human leukemic cells [25].
• Addition of 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB, 100 microM) or benzamil (100 microM) to the apical solution markedly reduced the secretin-induced I(sc) increase in the transient phase [26].

Analytical, diagnostic and therapeutic context of NPPB

• This location coincided with that of the NPPA locus; pulsed-field gel electrophoresis placed NPPA and NPPB within 50 kb of each other [9].
• In the case of small AVMs, surgery alone is a viable option; however, in the case of large AVMs, pre-operative embolisation is essential for prevention of NPPB (normal perfusion pressure breakthrough) [27].

References