scholarly journals Defining the role of CFTR channel blocker and ClC-2 activator in DNBS induced gastrointestinal inflammation

2021 ◽  
Vol 29 (4) ◽  
pp. 291-304
Author(s):  
Vijay Chidrawar ◽  
Bader Alsuwayt
Keyword(s):  
Channel Blocker ◽  
Gastrointestinal Inflammation

scholarly journals Tetrodotoxin: A New Strategy to Treat Visceral Pain?

Toxins ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 496
Author(s):  
Ana Campos-Ríos ◽  
Lola Rueda-Ruzafa ◽  
Salvador Herrera-Pérez ◽  
Paula Rivas-Ramírez ◽  
José Antonio Lamas
Keyword(s):  
Action Potentials ◽  
Channel Blocker ◽  
Visceral Pain ◽  
Visceral Hypersensitivity ◽  
Afferent Neurons ◽  
Sodium Channel Blocker ◽  
Voltage Gated Sodium Channels ◽  
New Strategy ◽  
Specific Receptors

Visceral pain is one of the most common symptoms associated with functional gastrointestinal (GI) disorders. Although the origin of these symptoms has not been clearly defined, the implication of both the central and peripheral nervous systems in visceral hypersensitivity is well established. The role of several pathways in visceral nociception has been explored, as well as the influence of specific receptors on afferent neurons, such as voltage-gated sodium channels (VGSCs). VGSCs initiate action potentials and dysfunction of these channels has recently been associated with painful GI conditions. Current treatments for visceral pain generally involve opioid based drugs, ≠≠which are associated with important side-effects and a loss of effectiveness or tolerance. Hence, efforts have been intensified to find new, more effective and longer-lasting therapies. The implication of VGSCs in visceral hypersensitivity has drawn attention to tetrodotoxin (TTX), a relatively selective sodium channel blocker, as a possible and promising molecule to treat visceral pain and related diseases. As such, here we will review the latest information regarding this toxin that is relevant to the treatment of visceral pain and the possible advantages that it may offer relative to other treatments, alone or in combination.

Enhanced role of K+ channels in relaxations of hypercholesterolemic rabbit carotid artery to NO

1995 ◽  
Vol 269 (3) ◽  
pp. H805-H811 ◽  
Author(s):  
S. Najibi ◽  
R. A. Cohen
Keyword(s):  
Carotid Artery ◽  
Sodium Nitroprusside ◽  
Channel Blocker ◽  
Isometric Tension ◽  
K Channel ◽  
K Channels ◽  
Rabbit Carotid Artery ◽  
Cyclic Monophosphate ◽  
Endothelium Dependent Relaxation

Endothelium-dependent relaxations to acetylcholine remain normal in the carotid artery of hypercholesterolemic rabbits, but unlike endothelium-dependent relaxations of normal rabbits, they are inhibited by charybdotoxin, a specific blocker of Ca(2+)-dependent K+ channels. Because nitric oxide (NO) is the mediator of endothelium-dependent relaxation and can activate Ca(2+)-dependent K+ channels directly or via guanosine 3',5'-cyclic monophosphate, the present study investigated the role of Ca(2+)-dependent K+ channels in relaxations caused by NO, sodium nitroprusside, and 8-bromoguanosine 3',5'-cyclic monophosphate (8-Brc-GMP) in hypercholesterolemic rabbit carotid artery. Isometric tension was measured in rabbit carotid artery denuded of endothelium from normal and hypercholesterolemic rabbits which were fed 0.5% cholesterol for 12 wk. Under control conditions, relaxations to all agents were similar in normal and hypercholesterolemic rabbit arteries. Charybdotoxin had no significant effect on relaxations of normal arteries to NO, sodium nitroprusside, or 8-BrcGMP, but the Ca(2+)-dependent K+ channel blocker significantly inhibited the relaxations caused by each of these agents in the arteries from hypercholesterolemic rabbits. By contrast, relaxations to the calcium channel blocker nifedipine were potentiated to a similar extent by charybdotoxin in both groups. In addition, arteries from hypercholesterolemic rabbits relaxed less than normal to sodium nitroprusside when contracted with depolarizing potassium solution. These results indicate that although nitrovasodilator relaxations are normal in the hypercholesterolemic rabbit carotid artery, they are mediated differently, and to a greater extent, by Ca(2+)-dependent K+ channels. These data also suggest that K+ channel-independent mechanism(s) are impaired in hypercholesterolemia.

scholarly journals The role of the calcium-sensing receptor in gastrointestinal inflammation

2016 ◽  
Vol 49 ◽  
pp. 44-51 ◽  
Author(s):  
Jennifer L. Owen ◽  
Sam X. Cheng ◽  
Yong Ge ◽  
Bikash Sahay ◽  
Mansour Mohamadzadeh
Keyword(s):  
Calcium Sensing Receptor ◽  
Calcium Sensing ◽  
Gastrointestinal Inflammation

scholarly journals Contributions of A2A and A2B adenosine receptors in coronary flow responses in relation to the KATP channel using A2B and A2A/2B double-knockout mice

2011 ◽  
Vol 301 (6) ◽  
pp. H2322-H2333 ◽  
Author(s):  
Maryam Sharifi Sanjani ◽  
Bunyen Teng ◽  
Thomas Krahn ◽  
Stephen Tilley ◽  
Catherine Ledent ◽  
...  
Keyword(s):  
Coronary Flow ◽  
Channel Blocker ◽  
Cardiovascular Disorders ◽  
Therapeutic Approaches ◽  
Double Knockout ◽  
Cgs 21680 ◽  
Pathological Conditions ◽  
Sch 58261 ◽  
Single Knockout

Adenosine plays a role in physiological and pathological conditions, and A2 adenosine receptor (AR) expression is modified in many cardiovascular disorders. In this study, we elucidated the role of the A2BAR and its relationship to the A2AAR in coronary flow (CF) changes using A2B single-knockout (KO) and A2A/2B double-KO (DKO) mice in a Langendorff setup. We used two approaches: 1) selective and nonselective AR agonists and antagonists and 2) A2AKO and A2BKO and A2A/2BDKO mice. BAY 60-6583 (a selective A2B agonist) had no effect on CF in A2BKO mice, whereas it significantly increased CF in wild-type (WT) mice (maximum of 23.3 ± 9 ml·min−1·g−1). 5′- N-ethylcarboxamido adenosine (NECA; a nonselective AR agonist) increased CF in A2BKO mice (maximum of 34.6 ± 4.7 ml·min−1·g−1) to a significantly higher degree compared with WT mice (maximum of 23.1 ± 2.1 ml·min−1·g−1). Also, CGS-21680 (a selective A2A agonist) increased CF in A2BKO mice (maximum of 29 ± 1.9 ml·min−1·g−1) to a significantly higher degree compared with WT mice (maximum of 25.1 ± 2.3 ml·min−1·g−1). SCH-58261 (an A2A-selective antagonist) inhibited the NECA-induced increase in CF to a significantly higher degree in A2BKO mice (19.3 ± 1.6 vs. 0.5 ± 0.4 ml·min−1·g−1) compared with WT mice (19 ± 3.5 vs. 3.6 ± 0.5 ml·min−1·g−1). NECA did not induce any increase in CF in A2A/2BDKO mice, whereas a significant increase was observed in WT mice (maximum of 23.1 ± 2.1 ml·min−1·g−1). Furthermore, the mitochondrial ATP-sensitive K+ (KATP) channel blocker 5-hydroxydecanoate had no effect on the NECA-induced increase in CF in WT mice, whereas the NECA-induced increase in CF in WT (17.6 ± 2 ml·min−1·g−1), A2AKO (12.5 ± 2.3 ml·min−1·g−1), and A2BKO (16.2 ± 0.8 ml·min−1·g−1) mice was significantly blunted by the KATP channel blocker glibenclamide (to 0.7 ± 0.7, 2.3 ± 1.1, and 0.9 ± 0.4 ml·min−1·g−1, respectively). Also, the CGS-21680-induced (22 ± 2.3 ml·min−1·g−1) and BAY 60-6583-induced (16.4 ± 1.60 ml·min−1·g−1) increase in CF in WT mice was significantly blunted by glibenclamide (to 1.2 ± 0.4 and 1.8 ± 1.2 ml·min−1·g−1, respectively). In conclusion, this is the first evidence supporting the compensatory upregulation of A2AARs in A2BKO mice and demonstrates that both A2AARs and A2BARs induce CF changes through KATP channels. These results identify AR-mediated CF responses that may lead to better therapeutic approaches for the treatment of cardiovascular disorders.

Severe beta blocker and calcium channel blocker overdose: Role of high dose insulin

2018 ◽  
Vol 36 (4) ◽  
pp. 736.e5-736.e6 ◽  
Author(s):  
Karan Seegobin ◽  
Satish Maharaj ◽  
Ansuya Deosaran ◽  
Pramod Reddy
Keyword(s):  
Calcium Channel ◽  
Calcium Channel Blocker ◽  
Beta Blocker ◽  
Channel Blocker ◽  
High Dose

scholarly journals Role of protein kinase C in Ca channel blocker-induced renal arteriolar dilation in spontaneously hypertensive rats

2005 ◽  
Vol 54 (2) ◽  
pp. 102-108 ◽  
Author(s):  
Koichi Hayashi ◽  
Shu Wakino ◽  
Yuri Ozawa ◽  
Koichiro Homma ◽  
Takeshi Kanda ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Spontaneously Hypertensive Rats ◽  
Channel Blocker ◽  
Ca Channel ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Kinase C

Functional role of sodium-calcium exchange in the regulation of renal vascular resistance

2001 ◽  
Vol 280 (1) ◽  
pp. F155-F161 ◽  
Author(s):  
Frank Schweda ◽  
Helga Seebauer ◽  
Bernhard K. Krämer ◽  
Armin Kurtz
Keyword(s):  
Calcium Channels ◽  
Vascular Resistance ◽  
Functional Role ◽  
Channel Blocker ◽  
Sodium Concentration ◽  
Renal Vascular Resistance ◽  
Partial Replacement ◽  
Chloride Channel Blocker ◽  
Renal Vascular

Our study aimed to assess a possible functional role of the Na+/Ca2+ exchanger in the regulation of renal vascular resistance (RVR). Therefore, we investigated the effects of an inhibition of the Na+/Ca2+ exchanger either by lowering the extracellular sodium concentration ([Na+]e) or, pharmacologically on RVR, by using isolated perfused rat kidneys. Graded decreases in [Na+]e led to dose-dependent increases in RVR to 4.3-fold (35 mM Na+). This vasoconstriction was markedly attenuated by lowering the extracellular calcium concentration, by the L-type calcium channel blocker amlodipine or by the chloride channel blocker niflumic acid. Further lowering of [Na+]e to 7 mM led to an increase in RVR to 7.5-fold. In this setting, amlodipine did not influence the magnitude but did influence the velocity of vasoconstriction. Pharmacological blockade of the Na+/Ca2+ exchanger with KB-R7943, benzamil, or nickel resulted in significant vasoconstriction (RVR 2.5-, 1.8-, and 4.2-fold of control, respectively). Our data suggest a functional role of the Na+/Ca2+ exchanger in the renal vascular bed. In conditions of partial replacement of [Na+]e, vasoconstriction is dependent on chloride and L-type calcium channels. A total replacement of [Na+]e leads to a vasoconstriction that is nearly independent of L-type calcium channels. This might be due to an active calcium transport into the cell by the Na+/Ca2+ exchanger.

Role of K+ channels in adrenal catecholamine secretion in anesthetized dogs

1998 ◽  
Vol 274 (4) ◽  
pp. R1125-R1130 ◽  
Author(s):  
Takahiro Nagayama ◽  
Kimiya Masada ◽  
Makoto Yoshida ◽  
Mizue Suzuki-Kusaba ◽  
Hiroaki Hisa ◽  
...  
Keyword(s):  
Channel Blocker ◽  
Splanchnic Nerve ◽  
Channel Blockers ◽  
Cholinergic Agonists ◽  
Voltage Dependent ◽  
Anesthetized Dogs ◽  
Splanchnic Nerve Stimulation ◽  
Mast Cell Degranulating ◽  
Small Conductance

We examined the role of K+ channels in the secretion of adrenal catecholamine (CA) in response to splanchnic nerve stimulation (SNS), acetylcholine (ACh), 1,1-dimethyl-4-phenyl-piperazinium (DMPP), and muscarine in anesthetized dogs. K+ channel blockers and the cholinergic agonists were infused and injected, respectively, into the adrenal gland. The voltage-dependent K+ channel (KA type) blocker mast cell degranulating (MCD) peptide infusion (10–100 ng/min) enhanced increases in CA output induced by SNS (1–3 Hz), but it did not affect increases in CA output induced by ACh (0.75–3 μg), DMPP (0.1–0.4 μg), or muscarine (0.5–2 μg). The small-conductance Ca2+-activated K+(SKCa) channel blocker scyllatoxin infusion (10–100 ng/min) enhanced the ACh-, DMPP-, and muscarine-induced increases in CA output, but it did not affect the SNS-induced increases in CA output. These results suggest that KA channels may play an inhibitory role in the regulation of adrenal CA secretion in response to SNS and that SKCa channels may play the same role in the secretion in response to exogenously applied cholinergic agonists.

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