Disease relevance of Lopac-N-170

• In the current study, we examined pial arteriolar responses to forskolin, dibutyryl-cAMP, NS-1619, and methionine (met)-enkephalin, activators of calcium-dependent K+ channels (K(Ca)) before and 1 hour after 10 minutes of total, global ischemia in anesthetized piglets [1].
• Additionally, we show that BK and NS-1619 significantly increased the density of transport vesicles in the cytoplasm of brain tumor capillary endothelia and tumor cells [2].

High impact information on Lopac-N-170

• ANG II (10 nM) decreased afferent arteriolar diameter by 44 +/- 4%, a response that was reduced by 30% during NS-1619 treatment; however, TEA failed to alter afferent constrictor responses to either ANG II or arginine vasopressin [3].
• 1. The effects of intracellular redox couples were investigated on the activation by voltage, Ca2+ and NS 1619 of maxi-K channels in enzymatically isolated smooth muscle cells from large pulmonary arteries of rabbits [4].
• NS 1619 also predisposed the maxi-K channel to open at more hyperpolarized membrane potentials [4].
• To test this hypothesis, we measured effects of NS-1619, a putative mtK(Ca) channel opener, and valinomycin, a K(+) ionophore, on mitochondrial respiration, DeltaPsi(m), and ROS generation in guinea pig heart mitochondria [5].
• Voltage-clamp recordings indicated that IBTX-sensitive currents were not enhanced to the extent observed in nondiabetic controls by increasing the Ca(2+) concentration in the pipette solution or the application of NS-1619 in myocytes from diabetic animals [6].

Biological context of Lopac-N-170

• In the isolated bladder strip, NS-1619 inhibited KCl-induced contractions in a concentration-dependent manner (IC50 = 12.2 +/- 3. 2 microM) [7].
• NS 1619 attenuated contraction of rings from rats at mid gestation and, to a lesser extent, at term gestation but accentuated contractions in rings from animals at term gestation in labor [8].
• Melatonin, like tetraethylammonium, significantly reduced vasodilation produced by NS-1619, an opener of BKCa channels [9].

Anatomical context of Lopac-N-170

• 8. NS 1619 (3-100 microM) produced a concentration-dependent inhibition of spontaneous activity in rat portal vein characterized by a reduction in the amplitude and duration of the tension waves [10].
• BK channel activation by NS-1619 is partially mediated by intracellular Ca2+ release in smooth muscle cells of porcine coronary artery [11].
• Activation of BKCa channels in acutely dissociated neurones from the rat ventromedial hypothalamus by NS 1619 [12].
• Ion channel modulation by NS 1619, the putative BKCa channel opener, in vascular smooth muscle [10].
• NS-1619 (a Ca(2+)-sensitive K(+) activator) elicited heightened effects in the aortas of pregnant animals receiving 0.9% NaCl supplementation [13].

Associations of Lopac-N-170 with other chemical compounds

• In contrast, coadministration of exogenous HSP-70 (1 mug/ml) potentiated dilation to cromakalim, CGRP, and NS-1619 [14].
• Unlike diazoxide (the opener of mitochondrial KATP channels), NS-1619 did not increase the expression of inducible or endothelial NOS [15].
• Cumulative concentration-response curves to low-affinity state beta1-AR agonists (CGP 12177, cyanopindolol or alprenolol) and to NS 1619, a large conductance Ca2+-activated K+ channels (BK) agonist were performed in denuded aortic rings isolated from control or treated Wistar Kyoto (WKY) rats or SHRs in different experimental conditions [16].
• NS 1619 reduced electrically stimulated contractile responses of rat vas deferens in a concentration-dependent manner, and charybdotoxin but not glibenclamide partially inhibited the effect of NS 1619 [17].
• The K(Ca) channel openers NS 1619 and 1-EBIO elicit relaxation effects that are not diminished after removal of the endothelium and are not inhibited by ouabain/Ba2+ [18].

Gene context of Lopac-N-170

• Under nonbrain injury conditions, topical coadministration of exogenous HSP-27 (1 mug/ml) blunted dilation to cromakalim, CGRP, and NS-1619 (10(-8) and 10(-6) M; cromakalim and CGRP are K(ATP) agonists and NS-1619 is a K(Ca) agonist) [14].
• This infarct-limiting effect of NS-1619 was associated with improvement in ventricular functional recovery after I/R [15].
• Furthermore, activation of BK(Ca) channels with NS-1619 was three times more effective at increasing outward current in cells from control versus IR animals [19].
• The effect of NS 1619 on the BK channel was dose-dependent, resulting in a shift of the activation curve by up to -50 mV towards negative membrane potentials [20].
• NS-1619, another BK channel opener, induced gradual but substantial change in F/F(K) even in native HEK, while the BK channel opening effect was detected [21].

Analytical, diagnostic and therapeutic context of Lopac-N-170

• Finally, whole-cell recordings of outward K(+) current detected a prominent iberiotoxin-sensitive BK(Ca) current in SMCs that was absent in ECs, and the BK(Ca) channel opener NS 1619 only enhanced K(+) current in the SMCs [22].
• Neither NS-1619 nor TEA altered agonist-induced constriction of the efferent arteriole [3].
• Adult male ICR mice were pretreated with the KCa-channel opener NS-1619 either 10 min or 24 h before 30 min of global ischemia and 60 min of reperfusion (I/R) in Langendorff mode [15].
• We were able to biochemically modulate one such protein marker, the calcium-dependent potassium (K(Ca)) channel, by using a specific K(Ca) channel agonist, NS-1619, to obtain sustained enhancement of selective drug delivery, including molecules of varying sizes, to tumors in rat syngeneic and xenograft brain tumor models [23].

References