Sulfur‐containing amino acids block stretch‐dependent K<sup>+</sup> channels and nitrergic responses in the murine colon

Park, Kyu Joo; Baker, Salah A.; Cho, Sang Yun; Sanders, Kenton M.; Koh, Sang Don

doi:10.1038/sj.bjp.0706154

Cited by 45 publications

(67 citation statements)

References 20 publications

(26 reference statements)

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“…The largest increase was observed in the amplitude of contraction. It has been shown previously that Hcy potentiates the depolarization of murine proximal colon cells, including the increase of the amplitude and frequency of spontaneous contractions of murine colonic stripes [26]. Our results supported this fi nding.…”

Section: Discussionsupporting

confidence: 91%

“…The gastrointestinal tract accounts for 25% of whole body transmethylation and transsulfuration pathways and is a prominent site of net Hcy release [15]. As reported previously, Hcy has been shown to change intestinal motility, in both a procinetic and inhibitory pattern, acting by modulation of nitrergic innervation or by potassium channels [26,39]. The present study was undertaken to expand upon those initial fi ndings and to assess the effect of D,L-homocysteine on the duodenal motility, especially mechanisms involving nitrergic and cholinergic pathways.…”

Section: Discussionmentioning

confidence: 73%

“…We thought that K+ ion channels may modulate the enteric neural inhibitory input to the duodenum. Park et al [26] suggested that spontaneous neural activity and release of NO tonically activated SDK channels. They showed that nitrergic responses to nerve stimulation were reduced by sulfur-containing amino acids.…”

Section: Discussionmentioning

confidence: 99%

“…Previously was demonstrated that the sulfur-containing amino acid methionine acted as a specifi c blocker of stretch dependent potassium channels and nitrergic responses in the murine colon [26].…”

Section: Introductionmentioning

confidence: 99%

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Different pathways involved in the stimulatory effects of homocysteine on rat duodenal smooth muscle

et al. 2017

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Recent studies have confi rmed that hyperhomocysteinemia is associated with gastrointestinal diseases; however, the direct effect of homocysteine on gastrointestinal reactivity still remains unknown. The aim of this study was to demonstrate how homocysteine may affect nitric oxide mediated duodenal relaxation and whether cholinergic receptors and K + channels take part in stimulating motility, as well as to explore whether oxidative stress is associated with homocysteine-mediated effects. Experiments were carried out on male rats, body mass 250-300 g. Two groups of animals were treated by i.p. application of saline and D,L-Hcy (0.6 μmol/g bm). After 2h of incubation, the duodenal segments were prepared for biochemical analysis and contractile response measurements in an organ bath with Tyrode's solution. Effects of TEA (10 mmol/L) and L-NAME (30 μmol/L) on duodenal contractility in the presence of D,L-Hcy (0.6 μmol/g bm) were investigated. Elevated homocysteine levels seem to be of crucial importance for the deterioration of contractility through nitric oxide mediated relaxation, and, in part, by activation of K + channels. Hcy showed direct promuscarinic effects, since 30 min pretreatment of rat duodenum signifi cantly enhanced the contractile effect of increasing concentrations of ACh (10 -9 -10 -2 mol/L). Catalase activity, superoxide dismutase, glutathione peroxidase and the total antioxidant system were reduced while the thiobarbituric acid-reactive substances level was elevated. Our data showed a consistent profi le of gastrointestinal injury elicited by sulfur-containing amino acid-homocysteine. This could contribute to explain, at least in part, the mechanisms involved in human gastrointestinal diseases associated to hyperhomocysteinemia.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 73%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Different pathways involved in the stimulatory effects of homocysteine on rat duodenal smooth muscle

et al. 2017

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“…60 Pharmacologically, sulfur-containing amino acids, such as L-cysteine, L-methionine, or DLhomocysteine block the SDK channel, cause SMC depolarization and muscle contraction. 61 Other compounds such as caffeine, ryanodine, and cyclopiazonic acid may also have similar effects. Thus the SDK channel is a another possible target for the treatment of GI dysmotility.…”

Section: 55mentioning

confidence: 99%

Targeting Ion Channels: An Important Therapeutic Implication in Gastrointestinal Dysmotility in Patients With Spinal Cord Injury

Radulovic

Anand

Korsten

et al. 2015

J Neurogastroenterol Motil

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Gastrointestinal (GI) dysmotility is a severe, and common complication in patients with spinal cord injury (SCI). Current therapeutic methods using acetylcholine analogs or laxative agents have unwanted side effects, besides often fail to have desired effect. Various ion channels such as ATP-sensitive potassium (KATP) channel, calcium ions (Ca 2+ )-activated potassium ions (K + ) channels, voltage-sensitive Ca 2+ channels and chloride ion (Cl − ) channels are abundantly expressed in GI tissues, and play an important role in regulating GI motility. The release of neurotransmitters from the enteric nerve terminal, innervating GI interstitial cells of Cajal (ICC), and smooth muscle cells (SMC), causes inactivation of K + and Cl − channels, increasing Ca 2+ influx into cytoplasm, resulting in membrane depolarization and smooth muscle contraction. Thus, agents directly regulating ion channels activity either in ICC or in SMC may affect GI peristalsis and would be potential therapeutic target for the treatment of GI dysmotility with SCI.

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Electrophysiology and pharmacology of tandem domain potassium channel TREK-1 related BDNF synthesis in rat astrocytes

Lü

Wang

Peng

et al. 2014

Naunyn-Schmiedeberg's Arch Pharmacol

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In the present study, the functional properties and pharmacology of two-pore domain potassium channel (K2P) TREK-1 in primary cultured rat brain astrocytes were investigated. Western blot, patch clamping techniques, and ELISA were used to detect the distribution and function of TREK-1 as well as the expression of brain-derived neurotrophic factor (BDNF) on the primary cultured astrocytes. It was shown that TREK-1 protein expressed in astrocytes was 2.4-fold higher than it was expressed in microglia. Single channel recording via patch clamping showed that the TREK-1 outward currents in astrocytes could be activated by arachidonic acid (AA) or chloroform with the conductance of 113 ± 14 and 120 ± 13 pS, respectively. The current was also sensitive to mechanical stretch and intracellular acidification. Negative pressure (-30 cm H2O) and acidification of intracellular solution (pH 6.8 or 6.3) both enhanced TREK-1 channel open probability significantly. Further pharmacological studies showed that TREK-1 antagonist penfluridol inhibited AA-induced currents, and both penfluridol and methionine (TREK-1 blockers) significantly increased BDNF level in astrocytes by 50 %. These results indicated that TREK-1 channel current was a major component of K2P currents in astrocytes. TREK-1 channels might play important roles in regulating the function of astrocytes and might be used as a drug target for neuroprotection.

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Sulfur‐containing amino acids block stretch‐dependent K⁺ channels and nitrergic responses in the murine colon

Cited by 45 publications

References 20 publications

Different pathways involved in the stimulatory effects of homocysteine on rat duodenal smooth muscle

Different pathways involved in the stimulatory effects of homocysteine on rat duodenal smooth muscle

Targeting Ion Channels: An Important Therapeutic Implication in Gastrointestinal Dysmotility in Patients With Spinal Cord Injury

Electrophysiology and pharmacology of tandem domain potassium channel TREK-1 related BDNF synthesis in rat astrocytes

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Sulfur‐containing amino acids block stretch‐dependent K+ channels and nitrergic responses in the murine colon

Cited by 45 publications

References 20 publications

Different pathways involved in the stimulatory effects of homocysteine on rat duodenal smooth muscle

Different pathways involved in the stimulatory effects of homocysteine on rat duodenal smooth muscle

Targeting Ion Channels: An Important Therapeutic Implication in Gastrointestinal Dysmotility in Patients With Spinal Cord Injury

Electrophysiology and pharmacology of tandem domain potassium channel TREK-1 related BDNF synthesis in rat astrocytes

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Sulfur‐containing amino acids block stretch‐dependent K⁺ channels and nitrergic responses in the murine colon