Effects of Grape Seed Proanthocyanidin on 5-Hydroxytryptamine3 Receptors in NCB-20 Neuroblastoma Cells

Cho, Hyeong-Seok; Jeun, Seung-Hyun; Kim, Ki‐Jung; Choi, Se Joon; Sung, Ki-Wug

doi:10.1248/bpb.34.1109

Cited by 3 publications

(6 citation statements)

References 32 publications

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“…To determine the direct effects of lamotrigine on 5-HT 3 receptor currents, we studied the concentration-dependent responses of lamotrigine (1~300 µM) on the currents activated by 3 µM of 5-HT, near EC 50 of 5-HT 3 receptor currents in our previous report [23]. Application of lamotrigine (300 µM) alone did not induce any current (data not shown).…”

Section: Resultsmentioning

confidence: 98%

“…NCB-20 neuroblastoma cells (kindly provided by Dr. Lovinger, National Institute on Alcohol Abuse and Alcoholism, USA) were maintained under conditions previously described conditions [23]. Frozen cell stocks were maintained in liquid nitrogen, and thawed as needed.…”

Section: Methodsmentioning

confidence: 99%

“…For whole-cell patch-clamp recordings, NCB-20 cells were plated on cover glasses (12 mm diameter; Fisher Scientific, Pittsburgh, PA, USA) and transferred to the recording chamber (RC-13, Warner Instruments, Hamden, CT, USA) mounted on the stage of an inverted microscope (IX70, Olympus, Tokyo, Japan) at room temperature (21~24℃), as previously described [23]. Cells were continuously perfused with an extracellular solution containing (in mM) 150 NaCl, 2.5 KCl, 2.5 CaCl 2 , 10 N -(2-hydroxyethyl)piperazine- N ′-2-ethansulfonic acid (HEPES), and 10 D-glucose (pH adjusted to 7.4 with NaOH and osmolality adjusted to 340 mOsm/kg with sucrose) at a rate of 2~3 ml/min through the theta glass micropipette (see below in Drug preparation and application) .…”

Section: Methodsmentioning

confidence: 99%

“…A fast drug application technique was used to induce the 5-HT 3 receptor currents and to evaluate the drug effects as previously described [23]. After establishing a whole-cell configuration, cells were lifted up and positioned in front of one side of theta glass micropipette, which was pulled from the theta glass tubing (Clark Borosilicate Theta, Warner Instruments; 2 mm outer diameter, 1.4 mm inner diameter, 0.2 mm septum thickness) to an outer diameter of ~300 µm, and continuously perfused with an extracellular solution.…”

Section: Methodsmentioning

confidence: 99%

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Lamotrigine, an antiepileptic drug, inhibits 5-HT₃receptor currents in NCB-20 neuroblastoma cells

Kim

Jeun

Sung

2017

Korean J Physiol Pharmacol

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Lamotrigine is an antiepileptic drug widely used to treat epileptic seizures. Using whole-cell voltage clamp recordings in combination with a fast drug application approach, we investigated the effects of lamotrigine on 5-hydroxytryptamine (5-HT)3 receptors in NCB-20 neuroblastoma cells. Co-application of lamotrigine (1~300 µM) resulted in a concentration-dependent reduction in peak amplitude of currents induced by 3 µM of 5-HT for an IC50 value of 28.2±3.6 µM with a Hill coefficient of 1.2±0.1. These peak amplitude decreases were accompanied by the rise slope reduction. In addition, 5-HT3-mediated currents evoked by 1 mM dopamine, a partial 5-HT3 receptor agonist, were inhibited by lamotrigine co-application. The EC50 of 5-HT for 5-HT3 receptor currents were shifted to the right by co-application of lamotrigine without a significant change of maximal effect. Currents activated by 5-HT and lamotrigine co-application in the presence of 1 min pretreatment of lamotrigine were similar to those activated by 5-HT and lamotrigine co-application alone. Moreover, subsequent application of lamotrigine in the presence of 5-HT and 5-hydroxyindole, known to attenuate 5-HT3 receptor desensitization, inhibited 5-HT3 receptor currents in a concentration-dependent manner. The deactivation of 5-HT3 receptor was delayed by washing with an external solution containing lamotrigine. Lamotrigine accelerated the desensitization process of 5-HT3 receptors. There was no voltage-dependency in the inhibitory effects of lamotrigine on the 5-HT3 receptor currents. These results indicate that lamotrigine inhibits 5-HT3-activated currents in a competitive manner by binding to the open state of the channels and blocking channel activation or accelerating receptor desensitization.

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Section: Resultsmentioning

confidence: 98%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Lamotrigine, an antiepileptic drug, inhibits 5-HT₃receptor currents in NCB-20 neuroblastoma cells

Kim

Jeun

Sung

2017

Korean J Physiol Pharmacol

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“…The extract reduced by 77% the morphine-induced vomiting and retching, suggesting that it could suppress the activation of sensory afferent nerve implicated in the emetic reflex (69). According to these observations, Li et al reported that a grape seed proanthocyanidin extract inhibits in a non-competitive manner the 5-hydroxytryptamine-3 receptors involved in the initiation and coordination of the vomiting reflex, in NCB-20 neuroblastoma cells (70). Taking together, these results suggest that PAC-containing extracts or foodstuffs could be used as a complementary medicine for the management of nausea/emesis, without the side effect usually associated with cannabinoid-based antiemetic agents.…”

Section: Pacs In the Stomachmentioning

confidence: 99%

The Gastrointestinal Tract as a Key Target Organ for the Health-Promoting Effects of Dietary Proanthocyanidins

et al. 2017

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Proanthocyanidins (PACs) are polymers of flavan-3-ols abundant in many vegetable foods and beverages widely consumed in the human diet. There is increasing evidence supporting the beneficial impact of dietary PACs in the prevention and nutritional management of non-communicable chronic diseases. It is considered that PACs with a degree of polymerization >3 remain unabsorbed in the gastrointestinal (GI) tract and accumulate in the colonic lumen. Accordingly, the GI tract may be considered as a key organ for the healthy-promoting effects of dietary PACs. PACs form non-specific complexes with salivary proteins in mouth, originating the sensation of astringency, and with dietary proteins, pancreatic enzymes, and nutrient transporters in the intestinal lumen, decreasing the digestion and absorption of carbohydrates, proteins, and lipids. They also exert antimicrobial activities, interfering with cariogenic or ulcerogenic pathogens in the mouth (Streptococcus mutans) and stomach (Helicobacter pylori), respectively. Through their antioxidant and antiinflammatory properties, PACs decrease inflammatory processes in animal model of gastric and colonic inflammation. Interestingly, they exert prebiotic activities, stimulating the growth of Lactobacillus spp. and Bifidobacterium spp. as well as some butyrate-producing bacteria in the colon. Finally, PACs are also metabolized by the gut microbiota, producing metabolites, mainly aromatic acids and valerolactones, which accumulate in the colon and/or are absorbed into the bloodstream. Accordingly, these compounds could display biological activities on the colonic epithelium or in extra-intestinal tissues and, therefore, contribute to part of the beneficial effects of dietary PACs.

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Tricyclic antidepressant amitriptyline inhibits 5-hydroxytryptamine 3 receptor currents in NCB-20 cells

Park

Myeong

Kim

et al. 2018

Korean J Physiol Pharmacol

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Amitriptyline, a tricyclic antidepressant, is commonly used to treat depression and neuropathic pain, but its mechanism is still unclear. We tested the effect of amitriptyline on 5-hydroxytryptamine 3 (5-HT3) receptor currents and studied its blocking mechanism because the clinical applications of amitriptyline overlapped with 5-HT3 receptor therapeutic potentials. Using a whole-cell voltage clamp method, we recorded the currents of the 5-HT3 receptor when 5-HT was applied alone or co-applied with amitriptyline in cultured NCB-20 neuroblastoma cells known to express 5-HT3 receptors. To elucidate the mechanism of amitriptyline, we simulated the 5-HT3 receptor currents using Berkeley Madonna® software and calculated the rate constants of the agonist binding and receptor transition steps. The 5-HT3 receptor currents were inhibited by amitriptyline in a concentration-dependent, voltage-independent manner, and a competitive mode. Amitriptyline accelerated the desensitization of the 5-HT3 receptor. When amitriptyline was applied before 5-HT treatment, the currents rose slowly until the end of 5-HT treatment. When amitriptyline was co-applied with 5-HT, currents rose and decayed rapidly. Peak current amplitudes were decreased in both applications. All macroscopic currents recorded in whole cell voltage clamping experiments were reproduced by simulation and the changes of rate constants by amitriptyline were correlated with macroscopic current recording data. These results suggest that amitriptyline blocks the 5-HT3 receptor by close and open state blocking mechanisms, in a competitive manner. We could expand an understanding of pharmacological mechanisms of amitriptyline related to the modulation of a 5-HT3 receptor, a potential target of neurologic and psychiatric diseases through this study.

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Effects of Grape Seed Proanthocyanidin on 5-Hydroxytryptamine3 Receptors in NCB-20 Neuroblastoma Cells

Cited by 3 publications

References 32 publications

Lamotrigine, an antiepileptic drug, inhibits 5-HT₃receptor currents in NCB-20 neuroblastoma cells

Lamotrigine, an antiepileptic drug, inhibits 5-HT₃receptor currents in NCB-20 neuroblastoma cells

The Gastrointestinal Tract as a Key Target Organ for the Health-Promoting Effects of Dietary Proanthocyanidins

Tricyclic antidepressant amitriptyline inhibits 5-hydroxytryptamine 3 receptor currents in NCB-20 cells

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Effects of Grape Seed Proanthocyanidin on 5-Hydroxytryptamine3 Receptors in NCB-20 Neuroblastoma Cells

Cited by 3 publications

References 32 publications

Lamotrigine, an antiepileptic drug, inhibits 5-HT3receptor currents in NCB-20 neuroblastoma cells

Lamotrigine, an antiepileptic drug, inhibits 5-HT3receptor currents in NCB-20 neuroblastoma cells

The Gastrointestinal Tract as a Key Target Organ for the Health-Promoting Effects of Dietary Proanthocyanidins

Tricyclic antidepressant amitriptyline inhibits 5-hydroxytryptamine 3 receptor currents in NCB-20 cells

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Product

Resources

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Lamotrigine, an antiepileptic drug, inhibits 5-HT₃receptor currents in NCB-20 neuroblastoma cells

Lamotrigine, an antiepileptic drug, inhibits 5-HT₃receptor currents in NCB-20 neuroblastoma cells