Inhibition of the serotonin-induced inward current by dextromethorphan in rat nodose ganglion neurons

Ishibashi, Hiroyuki; Eto, Kojiro; Arimura, Yukiko; Yamada, Jun; Hatano, Yoshiko; Nishikawa, Masazumi; Нода, Мами; Takahama, Kazuo

doi:10.1016/j.brainres.2006.04.036

Cited by 3 publications

(1 citation statement)

References 31 publications

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“…Previous reports indicate that rat nodal ganglion cells respond to various concentrations of hormones, including CCK, GLP1, PYY, and 5‐HT [ 31 , 32 , 33 , 34 ]. With similar concentrations to these findings, this study showed that CCK‐33, GLP1, PYY, GLP2, and 5‐HT led to amplified Ca 2+ levels in CCKAR‐, GLP1R‐, NPY2R‐, GLP2R‐, and HTR3A‐neurons, respectively.…”

Section: Discussionmentioning

confidence: 99%

Functional engineering of human iPSC‐derived parasympathetic neurons enhances responsiveness to gastrointestinal hormones

Akagi,

Takayama,

Nihashi

et al. 2023

FEBS Open Bio

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Food‐derived biological signals are transmitted to the brain via peripheral nerves through the paracrine activity of gastrointestinal (GI) hormones. The signal transduction circuit of the brain–gut axis has been analyzed in animals; however, species‐related differences and animal welfare concerns necessitate investigation using in vitro human experimental models. Here, we focused on the receptors of five GI hormones (CCK, GLP1, GLP2, PYY, and serotonin (5‐HT)), and established human induced pluripotent stem cell (iPSC) lines that functionally expressed each receptor. Compared to the original iPSCs, iPSCs expressing one of the receptors did not show any differences in global mRNA expression, genomic stability, or differentiation capacities of the three germ layers. We induced parasympathetic neurons from these established iPSC lines to assess vagus nerve activity. We generated GI hormone receptor‐expressing neurons (CCKAR, GLP1R, and NPY2R‐neuron) and tested their responsiveness to each ligand using Ca2+ imaging and microelectrode array recording. GI hormone receptor‐expressing neurons (GLP2R and HTR3A) were generated directly by gene induction into iPSC‐derived peripheral nerve progenitors. These receptor‐expressing neurons promise to contribute to a better understanding of how the body responds to GI hormones via the brain–gut axis, aid in drug development, and offer an alternative to animal studies.

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Section: Discussionmentioning

confidence: 99%

Functional engineering of human iPSC‐derived parasympathetic neurons enhances responsiveness to gastrointestinal hormones

Akagi,

Takayama,

Nihashi

et al. 2023

FEBS Open Bio

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The effect of zinc on glycinergic inhibitory postsynaptic currents in rat spinal dorsal horn neurons

et al. 2007

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Pharmacology of dextromethorphan: Relevance to dextromethorphan/quinidine (Nuedexta®) clinical use

Taylor¹,

Traynelis

Siffert

et al. 2016

Pharmacology & Therapeutics

154

157

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Dextromethorphan (DM) has been used for more than 50years as an over-the-counter antitussive. Studies have revealed a complex pharmacology of DM with mechanisms beyond blockade of N-methyl-d-aspartate (NMDA) receptors and inhibition of glutamate excitotoxicity, likely contributing to its pharmacological activity and clinical potential. DM is rapidly metabolized to dextrorphan, which has hampered the exploration of DM therapy separate from its metabolites. Coadministration of DM with a low dose of quinidine inhibits DM metabolism, yields greater bioavailability and enables more specific testing of the therapeutic properties of DM apart from its metabolites. The development of the drug combination DM hydrobromide and quinidine sulfate (DM/Q), with subsequent approval by the US Food and Drug Administration for pseudobulbar affect, led to renewed interest in understanding DM pharmacology. This review summarizes the interactions of DM with brain receptors and transporters and also considers its metabolic and pharmacokinetic properties. To assess the potential clinical relevance of these interactions, we provide an analysis comparing DM activity from in vitro functional assays with the estimated free drug DM concentrations in the brain following oral DM/Q administration. The findings suggest that DM/Q likely inhibits serotonin and norepinephrine reuptake and also blocks NMDA receptors with rapid kinetics. Use of DM/Q may also antagonize nicotinic acetylcholine receptors, particularly those composed of α3β4 subunits, and cause agonist activity at sigma-1 receptors.

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Inhibition of the serotonin-induced inward current by dextromethorphan in rat nodose ganglion neurons

Cited by 3 publications

References 31 publications

Functional engineering of human iPSC‐derived parasympathetic neurons enhances responsiveness to gastrointestinal hormones

Functional engineering of human iPSC‐derived parasympathetic neurons enhances responsiveness to gastrointestinal hormones

The effect of zinc on glycinergic inhibitory postsynaptic currents in rat spinal dorsal horn neurons

Pharmacology of dextromethorphan: Relevance to dextromethorphan/quinidine (Nuedexta®) clinical use

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