High K+-induced contraction requires depolarization-induced Ca2+ release from internal stores in rat gut smooth muscle

Kirschstein, Timo; Rehberg, Mirko; Bajorat, Rika; Tokay, Tursonjan; Porath, Katrin; Köhling, Rüdiger

doi:10.1038/aps.2009.98

Cited by 28 publications

(27 citation statements)

References 46 publications

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“…The 2 major types of voltage-gated potassium channels are the sustained delayed rectifier current and the transient A-type current. 86,87 The increased level of potassium can lead to depolarization of the cell membrane in smooth muscles, which is associated with the entry of extracellular calcium ions as well as stimulation of bowel contractions. It has been suggested that ryanodine and inositol triphosphate receptors are involved in depolarization-induced calcium currents in muscle cells.…”

Section: 81mentioning

confidence: 99%

The Role of Visceral Hypersensitivity in Irritable Bowel Syndrome: Pharmacological Targets and Novel Treatments

Farzaei

Bahramsoltani

Abdollahi

et al. 2016

J Neurogastroenterol Motil

151

122

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Irritable bowel syndrome (IBS) is the most common disorder referred to gastroenterologists and is characterized by altered bowel habits, abdominal pain, and bloating. Visceral hypersensitivity (VH) is a multifactorial process that may occur within the peripheral or central nervous systems and plays a principal role in the etiology of IBS symptoms. The pharmacological studies on selective drugs based on targeting specific ligands can provide novel therapies for modulation of persistent visceral hyperalgesia. The current paper reviews the cellular and molecular mechanisms underlying therapeutic targeting for providing future drugs to protect or treat visceroperception and pain sensitization in IBS patients. There are a wide range of mediators and receptors participating in visceral pain perception amongst which substances targeting afferent receptors are attractive sources of novel drugs. Novel therapeutic targets for the management of VH include compounds which alter gut-brain pathways and local neuroimmune pathways. Molecular mediators and receptors participating in pain perception and visceroperception include histamine-1 receptors, serotonin (5-hydrodytryptamine) receptors, transient receptor potential vanilloid type I, tachykinins ligands, opioid receptors, voltage-gated channels, tyrosine receptor kinase receptors, protease-activated receptors, adrenergic system ligands, cannabinoid receptors, sex hormones, and glutamate receptors which are discussed in the current review. Moreover, several plant-derived natural compounds with potential to alleviate VH in IBS have been highlighted. VH has an important role in the pathology and severity of complications in IBS. Therefore, managing VH can remarkably modulate the symptoms of IBS. More preclinical and clinical investigations are needed to provide efficacious and targeted medicines for the management of VH. (J Neurogastroenterol Motil 2016;22:558-574)

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Section: 81mentioning

confidence: 99%

The Role of Visceral Hypersensitivity in Irritable Bowel Syndrome: Pharmacological Targets and Novel Treatments

Farzaei

Bahramsoltani

Abdollahi

et al. 2016

J Neurogastroenterol Motil

151

122

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“…Before the start of the experiment, a stable baseline tone was achieved for at least 50 min. Under these conditions, both contractions and relaxations have been found to be very reproducible and to show low variance between different tissue specimens in previous studies [21,22] . Isometric contractions and relaxations of the smooth muscle strips induced by KCl or purinergic ligands were measured by force transducers (MLT0201, ADInstruments, Oxford, UK) and recorded with a bridge amplifier (ML224, ADInstruments) connected to an analog-to-digital converter (Powerlab 4/30, ADInstruments) and then analyzed by the Chart 5 software (ADInstruments).…”

Section: Isometric Contractions In Vitromentioning

confidence: 70%

“…The organ bath fluid was not corrected for osmolarity after the addition of KCl. However, the resulting increase in osmolarity was well tolerated by the preparations, and hyperosmotic control experiments with addition of the same amount of NaCl revealed relaxation of the smooth muscle rather than contraction [21] . Each gut preparation was tested with KCl for depolarization-induced contractions at the beginning and at the end of the experiment and was included in the study when the KCl-induced contraction at the end of the experiment was at least 50% of the initial response.…”

Section: Isometric Contractions In Vitromentioning

confidence: 93%

P2Y receptor-mediated transient relaxation of rat longitudinal ileum preparations involves phospholipase C activation, intracellular Ca2+ release and SK channel activation

et al. 2016

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Aim: Purinergic signaling plays a major role in the enteric nervous system, where it governs gut motility through a number of P2X and P2Y receptors. The aim of this study was to investigate the P2Y receptor-mediated motility in rat longitudinal ileum preparations. Methods: Ileum smooth muscle strips were prepared from rats, and fixed in an organ bath. Isometric contraction and relaxation responses of the muscle strips were measured with force transducers. Drugs were applied by adding of stock solutions to the organ bath to yield the individual final concentrations. Results: Application of the non-hydrolyzable P2 receptor agonists α,β-Me-ATP or 2-Me-S-ADP (10, 100 µmol/L) dose-dependently elicited a transient relaxation response followed by a sustained contraction. The relaxation response was largely blocked by SK channel blockers apamin (500 nmol/L) and UCL1684 (10 µmol/L), PLC inhibitor U73122 (100 µmol/L), IP 3 receptor blocker 2-APB (100 µmol/L) or sarcoendoplasmic Ca 2+ ATPase inhibitor thapsigargin (1 µmol/L), but not affected by atropine, NO synthase blocker L-NAME or tetrodotoxin. Furthermore, α,β-Me-ATP-induced relaxation was suppressed by P2Y 1 receptor antagonist MRS2179 (50 µmol/L) or P2Y 13 receptor antagonist MRS2211 (100 µmol/L), and was abolished by co-application of the two antagonists, whereas 2-Me-S-ADP-induced relaxation was abolished by P2Y 6 receptor antagonist MRS2578 (50 µmol/L). In addition, P2Y 1 receptor antagonist MRS2500 (1 µmol/L) not only abolished α,β-Me-ATP-induced relaxation, but also suppressed 2-Me-S-ADP-induced relaxation. Conclusion: P2Y receptor agonist-induced transient relaxation of rat ileum smooth muscle strips is mediated predominantly by P2Y 1 receptor, but also by P2Y 6 and P2Y 13 receptors, and involves PLC, IP 3 , Ca 2+ release and SK channel activation, but is independent of acetylcholine and NO release.

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“…Activation of the muscarinic receptor induces activation of a G proteincoupled receptor which activates phospholipase-C to produce inositol-1,4,5, triphosphate (IP3) and diacylglycerol (DAG). These molecules mediate Ca 2+ release or entry into smooth muscle cells (Macara and Rico, 1992;Bolton et al, 1999;Kirschstein et al, 2009). Thus, citral and LE may block the production of IP3 and/ or block the release of Ca 2+ from the storage sites.…”

Section: Discussionmentioning

confidence: 99%

“…Substances that inhibit the K + -induced contraction are considered as blockers of Ca 2+ influx (Brankovic et al, 2009;Kirschstein et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Spasmolytic effect of citral and extracts of Cymbopogon citratus on isolated rabbit ileum

Devi

Sim

Ismail

2011

J Smooth Muscle Res

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Cymbopogon citratus, commonly known as lemongrass, has been shown to have antioxidant, antimicrobial and chemo-protective properties. Citral, a monoterpenoid, is the major constituent of C. citratus that gives off a lemony scent and is postulated to be responsible for most of its actions. In addition, C. citratus has been traditionally used to treat gastrointestinal discomforts, however, the scientific evidence for this is still lacking. Thus, the aim of the present study was to investigate the effect of the extracts of various parts of C. citratus (leaves, stems and roots) and citral on the visceral smooth muscle activity of rabbit ileum. The effect of the test substances were tested on the spontaneous contraction, acetylcholine (ACh)-and KCl-induced contractions. Citral at doses between 0.061 mM to 15.6 mM and the extract of leaves at doses between 0.001 mg/mL to 1 mg/mL significantly reduced the spontaneous, ACh-and KCl-induced ileal contractions. When the ileum was incubated in K + -rich-Ca 2+ -free Tyrode's solution, it showed only minute contractions. However, the strength of contraction was increased with the addition of increasing concentrations of CaCl2. The presence of citral almost abolished the effect of adding CaCl2, while the leaf extract shifted the calcium concentration-response curve to the right, suggesting a calcium antagonistic effect. These results were similar to that elicited by verapamil, a known calcium channel blocker. In addition, the spasmolytic effect of citral was observed to be reduced by the nitric oxide synthase inhibitor, L-NAME. In conclusion, citral and the leaf extract of C. citratus exhibited spasmolytic activity and it appeared that they may act as calcium antagonists. Furthermore, the relaxant effect of citral, but not that of the leaf extract may be mediated by nitric oxide suggesting the presence of other chemical components in the leaf extract other than citral.

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High K+-induced contraction requires depolarization-induced Ca2+ release from internal stores in rat gut smooth muscle

Cited by 28 publications

References 46 publications

The Role of Visceral Hypersensitivity in Irritable Bowel Syndrome: Pharmacological Targets and Novel Treatments

The Role of Visceral Hypersensitivity in Irritable Bowel Syndrome: Pharmacological Targets and Novel Treatments

P2Y receptor-mediated transient relaxation of rat longitudinal ileum preparations involves phospholipase C activation, intracellular Ca2+ release and SK channel activation

Spasmolytic effect of citral and extracts of Cymbopogon citratus on isolated rabbit ileum

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