Read by QxMD icon Read

bk channel inhibitor

Barry D Kyle, Ramesh C Mishra, Andrew P Braun
Large conductance, Ca(2+)-activated K(+) (BK) channels control cerebrovascular tone; however, the regulatory processes influencing these channels remain poorly understood. Here, we investigate the cellular mechanisms underlying the enhancement of BK current in rat cerebral arteries by nitric oxide (NO) signaling. In isolated cerebral myocytes, BK current magnitude was reversibly increased by sodium nitroprusside (SNP, 100 μM) and sensitive to the BK channel inhibitor, penitrem-A (100 nM). Fostriecin (30 nM), a protein phosphatase type 2A (PP2A) inhibitor, significantly prolonged the SNP-induced augmentation of BK current and a similar effect was produced by sildenafil (30 nM), a phosphodiesterase 5 (PDE5) inhibitor...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
Jue Wu, Na Li, Yanping Liu, Weisheng Li, Axin He, Di Zhu, Xueqin Feng, Bailin Liu, Ruixiu Shi, Yujuan Zhang, Juanxiu Lv, Zhice Xu
SCOPE: High salt (HS) diets are related to cardiovascular diseases, and prenatal HS was suggested to increase risks of coronary artery diseases in the offspring. This study tested the hypothesis that prenatal HS may influence Adenosine-induced vasodilatation via PKA pathway in coronary arteries. METHODS AND RESULTS: Sprague-Dawley rats were fed with 8% salt diet for gestation, the control was fed with 0.3% salt diet. Coronary arteries from male adult offspring were tested for K(+) channels and Adenosine signal pathways...
January 29, 2017: Molecular Nutrition & Food Research
Cibele Rocha-Resende, Nádia Miricéia Leão, Maria Elena de Lima, Robson Augusto Santos, Adriano Monteiro de Castro Pimenta, Thiago Verano-Braga
Cryptome is as a subset of a given proteome containing bioactive cryptides embedded in larger peptides or proteins. We pinpointed a striking sequence similarity between two peptides from the Tityus serrulatus venom: Ts10 (KKDGYPVEYDRAY) and the N-terminal of Ts3 (KKDGYPVEYDNCAY). Ts3 (former Tityustoxin or TsIV) is an α-neurotoxin acting on voltage-gated sodium channels while Ts10 (former Peptide T) is a bradykinin-potentiating peptide and was originally reported as inhibitor of the angiotensin-converting enzyme (ACEi)...
December 29, 2016: Peptides
Karina P Abrahao, Jessica H Chancey, C Savio Chan, David M Lovinger
Although ethanol is one of the most widely used drugs, we still lack a full understanding of which neuronal subtypes are affected by this drug. Pacemaker neurons exert powerful control over brain circuit function, but little is known about ethanol effects on these types of neurons. Neurons in the external globus pallidus (GPe) generate pacemaker activity that controls basal ganglia, circuitry associated with habitual and compulsive drug use. We performed patch-clamp recordings from GPe neurons and found that bath application of ethanol dose-dependently decreased the firing rate of low-frequency GPe neurons, but did not alter the firing of high-frequency neurons...
December 14, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Isabella Salzer, Enkhbileg Gantumur, Arsalan Yousuf, Stefan Boehm
Serotonin (5HT) is a constituent of the so-called "inflammatory soup" that sensitizes nociceptors during inflammation. Nevertheless, receptors and signaling mechanisms that mediate an excitation of dorsal root ganglion (DRG) neurons by 5HT remained controversial. Therefore, capsaicin-sensitive nociceptive neurons dissociated from rat DRGs were used to investigate effects of 5HT on membrane excitability and currents through ligand- as well as voltage-gated ion channels. In 58% of the neurons tested, 5HT increased action potential firing, an effect that was abolished by the 5HT2 receptor antagonist ritanserin, but not by the 5HT3 antagonist tropisetron...
November 2016: Neuropharmacology
Hiroaki Takagi, Hikaru Hashitani
The modulation of spontaneous excitability in detrusor smooth muscle (DSM) upon the pharmacological activation of different populations of K(+) channels was investigated. Effects of distinct K(+) channel openers on spontaneous action potentials in DSM of the guinea-pig bladder were examined using intracellular microelectrode techniques. NS1619 (10μM), a large conductance Ca(2+)-activated K(+) (BK) channel opener, transiently increased action potential frequency and then prevented their generation without hyperpolarizing the membrane in a manner sensitive to iberiotoxin (IbTX, 100nM)...
October 15, 2016: European Journal of Pharmacology
Zhoufeng Zhu, Jiaqi Tang, Xiuwen Zhou, Sharon Xiang, Xiaolin Zhu, Na Li, Ruixiu Shi, Yuan Zhong, Lubo Zhang, Miao Sun, Zhice Xu
We recently demonstrated that acetylcholine (ACh) produced reliable vasoconstrictions in the umbilical cords. This study investigated the possible mechanisms with different antagonists. ACh-mediated vasoconstrictions were decreased by voltage-operated calcium (Ca(2+)) channels antagonist nifedipine or inositol-1,4,5-trisphosphate-mediated Ca(2+) release antagonist 2-aminoethyl diphenylborinate, indicating that both extracellular and intracellular calcium modulated the ACh-stimulated umbilical contraction. Intracellular Ca(2+) concentrations were increased simultaneously with vasoconstrictions by ACh in the umbilical vessels...
July 12, 2016: Reproductive Toxicology
Yoshinori Hayashi, Saori Morinaga, Xia Liu, Jing Zhang, Zhou Wu, Takeshi Yokoyama, Hiroshi Nakanishi
Prostaglandin E2 (PGE2), a major metabolite of arachidonic acid produced by cyclooxygenase pathways, exerts its bioactive responses by activating four E-prostanoid receptor subtypes, EP1, EP2, EP3, and EP4. PGE2 enables modulating N-methyl-D-aspartate (NMDA) receptor-mediated responses. However, the effect of E-prostanoid receptor agonists on large-conductance Ca(2+)-activated K(+) (BK) channels, which are functionally coupled with NMDA receptors, remains unclear. Here, we showed that EP2 receptor-mediated signaling pathways increased NMDA-induced outward currents (I NMDA-OUT), which are associated with the BK channel activation...
2016: Mediators of Inflammation
G J Kaczorowski, M L Garcia
High conductance, calcium-activated potassium (BK) channels (KCa1.1) are important in regulating physiologic responses in many types of tissues and, as such, present opportunities for development of new therapeutic agents. Both channel agonists and inhibitors could have therapeutic utility, depending on medical application under consideration. However, characterization of molecular pharmacology of BK channels is incomplete and has been difficult to accomplish because of paucity of chemical leads that are acceptable templates for Medicinal Chemistry investigation...
2016: International Review of Neurobiology
Dongyang Huang, Ce Liang, Fan Zhang, Hongchao Men, Xiaona Du, Nikita Gamper, Hailin Zhang
T-type Ca(2+) channels are important regulators of peripheral sensory neuron excitability. Accordingly, T-type Ca(2+) currents are often increased in various pathological pain conditions, such as inflammation or nerve injury. Here we investigated effects of inflammation on functional expression of T-type Ca(2+) channels in small-diameter cultured dorsal root ganglion (DRG) neurons. We found that overnight treatment of DRG cultures with a cocktail of inflammatory mediators bradykinin (BK), adenosine triphosphate (ATP), norepinephrine (NE) and prostaglandin E2 (PGE2) strongly increased the population size of the small-diameter neurons displaying low-voltage activated (LVA, T-type) Ca(2+) currents while having no effect on the peak LVA current amplitude...
April 29, 2016: Biochemical and Biophysical Research Communications
Thomas M Leurgans, Maria Bloksgaard, Jonathan R Brewer, Luis A Bagatolli, Maise H Fredgart, Kristoffer Rosenstand, Maria L Hansen, Lars M Rasmussen, Akhmadjon Irmukhamedov, Jo Gr De Mey
BACKGROUND AND PURPOSE: We tested the hypothesis that in resistance arteries from cardiovascular disease (CVD) patients, effects of an endothelium-dependent vasodilator depend on the contractile stimulus. EXPERIMENTAL APPROACH: Arteries dissected from parietal pericardium of cardiothoracic surgery patients were studied by myography and imaging techniques. Segments were sub-maximally contracted by K(+) , the TxA2 analogue U46619 or endothelin-1 (ET-1). KEY RESULTS: Relaxing effects of Na-nitroprusside were comparable, but those of bradykinin (BK) were bigger in the presence of ET-1 compared with K(+) or U46619...
May 2016: British Journal of Pharmacology
Wenkuan Xin, Ning Li, Vitor S Fernandes, Biao Chen, Eric S Rovner, Georgi V Petkov
Large-conductance Ca(2+)-activated K(+) (BK) channels are critical regulators of detrusor smooth muscle (DSM) function. We aimed to investigate phosphodiesterase type 1 (PDE1) interactions with BK channels in human DSM to determine the mechanism by which PDE1 regulates human urinary bladder physiology. A combined electrophysiological, functional, and pharmacological approach was applied using human DSM specimens obtained from open bladder surgeries. The perforated whole cell patch-clamp technique was used to record transient BK currents (TBKCs) and the cell membrane potential in freshly isolated human DSM cells in combination with the selective PDE1 inhibitor, 8-methoxymethyl-3-isobutyl-1-methylxanthine (8MM-IBMX)...
May 15, 2016: American Journal of Physiology. Renal Physiology
Xingjuan Chen, Wennan Li, S Christopher Hiett, Alexander G Obukhov
Voltage-gated Kv7 channels are inhibited by agonists of Gq-protein-coupled receptors, such as histamine. Recent works have provided evidence that inhibition of vascular Kv7 channels may trigger vessel contractions. In this study, we investigated how Kv7 activity modulates the histamine-induced contractions in "healthy" and metabolic syndrome (MetS) pig right coronary arteries (CAs). We performed isometric tension and immunohistochemical studies with domestic, lean Ossabaw, and MetS Ossabaw pig CAs. We found that neither the Kv7...
2016: PloS One
Sujay V Kharade, Daniel Flores, Craig W Lindsley, Lisa M Satlin, Jerod S Denton
Diuretics acting on specific nephron segments to inhibit Na+ reabsorption have been used clinically for decades; however, drug interactions, tolerance, and derangements in serum K(+) complicate their use to achieve target blood pressure. ROMK is an attractive diuretic target, in part, because its inhibition is postulated to indirectly inhibit the bumetanide-sensitive Na(+)-K(+)-2Cl- co-transporter, NKCC2, and the amiloride- and benzamil-sensitive epithelial Na(+) channel, ENaC. The development of small-molecule ROMK inhibitors has created opportunities for exploring the physiological responses to ROMK inhibition...
December 9, 2015: American Journal of Physiology. Renal Physiology
Aaron Provence, Kiril L Hristov, Shankar P Parajuli, Georgi V Petkov
Estrogen replacement therapies have been suggested to be beneficial in alleviating symptoms of overactive bladder. However, the precise regulatory mechanisms of estrogen in urinary bladder smooth muscle (UBSM) at the cellular level remain unknown. Large conductance voltage- and Ca2+-activated K+ (BK) channels, which are key regulators of UBSM function, are suggested to be non-genomic targets of estrogens. This study provides an electrophysiological investigation into the role of UBSM BK channels as direct targets for 17β-estradiol, the principle estrogen in human circulation...
2015: PloS One
Oleksiy Gryshchenko, Julia V Gerasimenko, Oleg V Gerasimenko, Ole H Petersen
KEY POINTS: Bradykinin may play a role in the autodigestive disease acute pancreatitis, but little is known about its pancreatic actions. In this study, we have investigated bradykinin-elicited Ca(2+) signal generation in normal mouse pancreatic lobules. We found complete separation of Ca(2+) signalling between pancreatic acinar (PACs) and stellate cells (PSCs). Pathophysiologically relevant bradykinin concentrations consistently evoked Ca(2+) signals, via B2 receptors, in PSCs but never in neighbouring PACs, whereas cholecystokinin, consistently evoking Ca(2+) signals in PACs, never elicited Ca(2+) signals in PSCs...
January 15, 2016: Journal of Physiology
Dahis Manzanares, Stefanie Krick, Nathalie Baumlin, John S Dennis, Jean Tyrrell, Robert Tarran, Matthias Salathe
Transforming growth factor β1 (TGF-β1) is not only elevated in airways of cystic fibrosis (CF) patients, whose airways are characterized by abnormal ion transport and mucociliary clearance, but TGF-β1 is also associated with worse clinical outcomes. Effective mucociliary clearance depends on adequate airway hydration, governed by ion transport. Apically expressed, large-conductance, Ca(2+)- and voltage-dependent K(+) (BK) channels play an important role in this process. In this study, TGF-β1 decreased airway surface liquid volume, ciliary beat frequency, and BK activity in fully differentiated CF bronchial epithelial cells by reducing mRNA expression of the BK γ subunit leucine-rich repeat-containing protein 26 (LRRC26) and its function...
October 16, 2015: Journal of Biological Chemistry
Richard L Pye, Eric J Dunn, Ellen M Ricker, Jennifer G Jurcsisn, Barbara L Barr, Christopher N Wyatt
Obesity related pathologies are the health care crisis of our generation. The fat cell derived adipokine leptin has been shown to be a central stimulant of respiration. Very high levels of leptin, however, are associated with the depressed ventilatory phenotype observed in obesity hypoventilation syndrome. Leptin receptors have been identified on carotid body type I cells but how their activation might influence the physiology of these cells is not known.The acute application of leptin evoked calcium signaling responses in isolated type I cells...
2015: Advances in Experimental Medicine and Biology
Daniela Gavello, David Vandael, Sara Gosso, Emilio Carbone, Valentina Carabelli
KEY POINTS: Leptin is an adipokine produced by the adipose tissue regulating body weight through its appetite-suppressing effect and, as such, exerts a relevant action on the adipo-adrenal axis. Leptin has a dual action on adrenal mouse chromaffin cells both at rest and during stimulation. At rest, the adipokine inhibits the spontaneous firing of most cells by enhancing the probability of BK channel opening through the phosphoinositide 3-kinase signalling cascade. This inhibitory effect is absent in db(-) /db(-) mice deprived of Ob receptors...
November 15, 2015: Journal of Physiology
Gareth L Evans, Laura G Caller, Victoria Foster, Colin M Crump
BK polyomavirus (BKPyV) is a member of a family of potentially oncogenic viruses, whose reactivation can cause severe pathological conditions in transplant patients, leading to graft rejection. As with many non-enveloped viruses, it is assumed that virus release occurs through lysis of the host cell. We now show the first evidence for a non-lytic release pathway for BKPyV and that this pathway can be blocked by the anion channel inhibitor DIDS. Our data show a dose-dependent effect of DIDS on the release of BKPyV virions...
August 2015: Open Biology
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"