Disease relevance of C13840

• Chlorzoxazone or 1-EBIO increases Na(+) absorption across cystic fibrosis airway epithelial cells [1].
• The effects of 1-ethyl-2-benzimidazolinone (1-EBIO) and riluzole on human prostate cancer cells, LNCaP and PC-3, were evaluated using rubidium (86Rb(+)) efflux and proliferation assays [2].

Psychiatry related information on C13840

• Accordingly, this study has investigated the therapeutic potential of 1-EBIO using a range of in vivo seizure models, and assessed the adverse effect liability with the rotarod and locomotor activity paradigms [3].
• 1-EBIO was found to be effective at reducing seizure incidence in mice following maximal electroshock (ED(50) 36.0 mg/kg) as well as increasing the threshold to electrically- and pentylenetetrazole-induced seizures (TID(10)s 7.3 and 21.5 mg/kg, respectively) [3].

High impact information on C13840

• The effects of 1-EBIO and apamin are independent of the NADPH oxidase pathway, as demonstrated by using a PLB-985 cell line lacking the gp91phox subunit [4].
• Consistent with the enhanced ROS production and K(+) efflux mediated by 1-EBIO, we found that this SK opener increased apoptosis of PLB-985 cells [4].
• We report here that 1-ethyl-2-benzimidazolinone (1-EBIO), an activator of Ca(2+)-activated potassium channels of small conductance (SK) and intermediate conductance (IK), causes production of superoxide and hydrogen peroxide by neutrophils and granulocyte-differentiated PLB-985 cells [4].
• The elucidation of SK channel function has recently benefited from the discovery of SK channel enhancers, the prototype of which is 1-EBIO [5].
• After 3 days of treatment with 1-EBIO, mRNA levels of hIK1 were substantially diminished and no channel activity was detected [6].

Biological context of C13840

• Because the down-regulation of hIK1 bears immediate significance on the biological fate of keratinocytes, 1-EBIO and related compounds might emerge as potent tools to influence the proliferation of various non-excitable cells endowed with IK channels [6].
• In sham-operated rats, 1-ethyl-2-benzimidazolinone (1-EBIO), a selective opener of endothelial small and intermediate K(Ca), induced a substantial EDHF-mediated vasodilation, which was greatly reduced in hypertensive 5/6 nephrectomy rats and in normotensive 5/6 nephrectomy rats [7].
• Despite the prolongation of the outward current pulses by 1-EBIO, continuous action potential discharge became more regular, although its frequency declined [8].
• 5 1-EBIO activated a transient outward K(+) current and hyperpolarized the membrane potential by about 13 mV [9].
• Forskolin, UTP, 1-ethyl-2-benzimidazolinone (1-EBIO), NS004, 8-methoxypsoralen (Methoxsalen; 8-MOP), and genistein were evaluated for their effects on ion transport across primary cultures of human bronchial epithelium (HBE) expressing wild-type (wt HBE) and DeltaF508 (DeltaF-HBE) cystic fibrosis transmembrane conductance regulator [10].

Anatomical context of C13840

• OBJECTIVE: To confirm the identity of this channel as iKCA1 in human lung mast cells and to examine the effect of an iKCA1 opener, 1-ethyl-2-benzimidazolinone (1-EBIO), on Ca2+ influx and degranulation after IgE-dependent activation [11].
• The increased IKCa1 expression levels following exposure to high levels of LSS resulted in enhanced IK(Ca) whole-cell currents and in an increased hyperpolarization of the endothelium in response to ATP and the IK(Ca) opener 1-EBIO [12].
• 3. In endothelium-intact arteries, smooth muscle relaxation to 1-EBIO was not altered by either of the potassium channel blockers ChTX (100 nM; n=7), or IbTX (100 nM; n=4), or raised extracellular K(+) (25 mM) [13].
• 4. In freshly isolated mesenteric endothelial cells, 1-EBIO (600 microM) evoked a ChTX-sensitive outward K-current [13].
• Experiments were conducted to determine whether the Cl- secretagogue, 1-ethyl-2-benzimidazolinone (EBIO), stimulates Cl- transport in the rabbit conjunctival epithelium [14].

Associations of C13840 with other chemical compounds

• The iKCA1 opener 1-EBIO induced iKCA1 currents in 89% of human peripheral blood-derived mast cells, 12% of fresh HLMCs, and 67% of LTHLMCs, which were blocked by the iKCA1 blockers clotrimazole and TRAM-34 [11].
• 4. Using sharp micro-electrodes, the hyperpolarization of both the smooth muscle and the endothelium induced by 1-EBIO or by acetylcholine was unaffected by 100 nM iberiotoxin [15].
• Further investigation of endothelium-derived hyperpolarizing factor (EDHF) in rat hepatic artery: studies using 1-EBIO and ouabain [15].
• In contrast, 1-EBIO had no effect on smooth muscle cell conductance whereas NS 1619 (33 microM) stimulated an outward current while having no effect on the endothelial cells [13].
• 4. Hyperpolarizations of intact endothelium elicited by substance P (100 nM; 26.1+/-0.7 mV) were reduced by apamin (100 nM; 17.0+/-1.8 mV) whereas those to 1-ethyl-2-benzimidazolinone (1-EBIO, 600 microM, 21.0+/-0.3 mV) were unaffected (21.7+/-0.8 mV) [16].

Gene context of C13840

• Transient expression of KCNN4 cloned from H441 cells conferred a Ca(2+)- and 1-EBIO-sensitive K(+) conductance on Chinese hamster ovary cells, but this channel was inactive when [Ca(2+)](i) was <0.2 muM [17].
• To examine this issue, we have used the acute hippocampal slice model of epileptiform activity to investigate the effects of an enhancer of SK channel activity, 1-ethyl-benzimidazolinone (EBIO) [18].
• Electrophysiological investigations showed that expression of amino acids 1-299 of SK3 (SK3N_299) modified the 1-EBIO pharmacology of endogenous SK3 channels in PC12 cells without affecting the Ca(2+)-sensitvity [19].
• The K+ channel opener 1-ethyl-2-benzimidazolinone further increased CaCC-mediated Cl- secretion in normal and CF tissues [20].
• Salbutamol (1-10 microM) inhibited iKCa1 currents following activation with both anti-IgE and the iKCa1 opener 1-EBIO, and was reversed by removing salbutamol or by the addition of the selective beta2-adrenoceptor antagonist and inverse agonist ICI 118551 [21].

Analytical, diagnostic and therapeutic context of C13840

• Perfusion at the intracellular face of the cell, of an opener of intermediate conductance K(Ca) channel, 500 micro M 1-ethyl-benzimidazolinone (1-EBIO) increased the channel activity by about 4.5 fold [9].
• We investigated the effects of 1-ethyl-2-benzimidazolinone (1-EBIO) on ion transport in the mouse jejunum through the use of the short-circuit (Isc) current technique and the application of the patch-clamp technique to isolated jejunal crypts [22].

References