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State-of-the-Art Molecular Pharmacology in Japan
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State-of-the-Art Molecular Pharmacology in Japan

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pharmacology".

Deadline for manuscript submissions: closed (31 October 2022) | Viewed by 6031

Special Issue Editor

Prof. Dr. Takeo Nakanishi

E-Mail Website
Collection Editor
Faculty of Pharmacy, Takasaki University of Health and Welfare, 60 Nakaorui-machi, Takasaki-shi 370-0033, Japan
Interests: cancer; chemotherapy; drug-resistance; pharmacology; transporter; gene expression; pharmacokinetics; inflammation; prostaglandin
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Pharmacology is a discipline that deals with interactions between natural, semisynthetic, and fully (bio)synthetic therapeutic agents at the cellular and organismal levels, ranging from small molecules to macromolecules such as proteins and antibodies. Thus, this subject is positioned at the interface of pharmacy/chemistry and physiology/pathophysiology in their broadest senses, operating at various organizational levels, such as the molecular, subcellular, cellular, organ, and systemic platforms. Molecular pharmacology investigates the molecular mode of action of therapeutic agents using cellular, genetic, and molecular biology approaches, and is among the most rapidly developing fields of pharmacology.

Original research and review articles concerning molecular pharmacology are invited for submission to this Topical Collection, the “Molecular Pharmacology” Section aiming to publish the latest developments in cellular and molecular pharmacology with a major emphasis on the mechanism of action of novel drugs, innovative pharmacological technologies, cell signaling, transduction pathway analyses, genomics, proteomics, and metabolomics applications to study drug actions. An additional focus will be the way in which normal biological function is illuminated by the knowledge of drug action at the cellular and molecular level.

This Topical Collection is committed to providing an overview of the macromolecular sciences and technologies in Japan, there being a large number of research teams from different institutions and universities currently working together and devoting considerable efforts to develop and study molecular pharmacology.

Prof. Dr. Takeo Nakanishi
Collection Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • signal transduction
  • receptor
  • membrane transporter
  • animal models
  • preclinical
  • pharmacodynamics
  • pharmacokinetics
  • biopharmaceutics
  • drug development
  • drug metabolism

Published Papers (3 papers)

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Research

13 pages, 2653 KiB  
Article
Measurement of Hepatic CYP3A4 and 2D6 Activity Using Radioiodine-Labeled O-Desmethylvenlafaxine
by Asuka Mizutani, Masato Kobayashi, Riku Aibe, Yuka Muranaka, Kodai Nishi, Masanori Kitamura, Chie Suzuki, Ryuichi Nishii, Naoto Shikano, Yasuhiro Magata, Yasushi Ishida, Munetaka Kunishima and Keiichi Kawai
Int. J. Mol. Sci. 2022, 23(19), 11458; https://doi.org/10.3390/ijms231911458 - 28 Sep 2022
Viewed by 1327
Abstract
Drug metabolizing enzyme activity is affected by various factors such as drug–drug interactions, and a method to quantify drug metabolizing enzyme activity in real time is needed. In this study, we developed a novel radiopharmaceutical for quantitative imaging to estimate hepatic CYP3A4 and [...] Read more.
Drug metabolizing enzyme activity is affected by various factors such as drug–drug interactions, and a method to quantify drug metabolizing enzyme activity in real time is needed. In this study, we developed a novel radiopharmaceutical for quantitative imaging to estimate hepatic CYP3A4 and CYP2D6 activity. Iodine-123- and 125-labeled O-desmethylvenlafaxine (123/125I-ODV) was obtained with high labeling and purity, and its metabolism was found to strongly involve CYP3A4 and CYP2D6. SPECT imaging in normal mice showed that the administered 123I-ODV accumulated early in the liver and was excreted into the gallbladder, as evaluated by time activity curves. In its biological distribution, 125I-ODV administered to mice accumulated early in the liver, and only the metabolite of 125I-ODV was quickly excreted into the bile. In CYP3A4- and CYP2D6-inhibited model mice, the accumulation in bile decreased more than in normal mice, indicating inhibition of metabolite production. These results indicated that imaging and quantifying the accumulation of radioactive metabolites in excretory organs will aid in determining the dosages of various drugs metabolized by CYP3A4 and CYP2D6 for individualized medicine. Thus, 123/125I-ODV has the potential to direct, comprehensive detection and measurement of hepatic CYP3A4 and CYP2D6 activity by a simple and less invasive approach. Full article
(This article belongs to the Special Issue State-of-the-Art Molecular Pharmacology in Japan)
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17 pages, 2719 KiB  
Article
Reactive Oxygen Species Cause Exercise-Induced Angina in a Myocardial Ischaemia-Reperfusion Injury Model
by Xiaohang Wang, Hirosato Kanda, Takeshi Tsujino, Yoko Kogure, Feng Zhu, Satoshi Yamamoto, Taichi Sakaguchi, Koichi Noguchi and Yi Dai
Int. J. Mol. Sci. 2022, 23(5), 2820; https://doi.org/10.3390/ijms23052820 - 04 Mar 2022
Cited by 1 | Viewed by 2050
Abstract
Percutaneous coronary intervention (PCI) effectively treats obstructive coronary artery syndrome. However, 30–40% patients continue to have angina after a successful PCI, thereby reducing patient satisfaction. The mechanisms underlying persistent angina after revascularisation therapy are still poorly understood; hence, the treatment or guideline for [...] Read more.
Percutaneous coronary intervention (PCI) effectively treats obstructive coronary artery syndrome. However, 30–40% patients continue to have angina after a successful PCI, thereby reducing patient satisfaction. The mechanisms underlying persistent angina after revascularisation therapy are still poorly understood; hence, the treatment or guideline for post-PCI angina remains unestablished. Thus, this study aimed to investigate the mechanisms underlying effort angina in animals following myocardial ischaemia-reperfusion (I/R) injury. Phosphorylated extracellular signal-regulated kinase (p-ERK), a marker for painful stimulation-induced neuronal activation, was used for the investigation. After a forced treadmill exercise (FTE), the number of p-ERK-expressing neurons increased in the superficial dorsal horn of the I/R model animals. Moreover, FTE evoked hydrogen peroxide (H2O2) production in the I/R-injured heart, inducing angina through TRPA1 activation on cardiac sensory fibres. Notably, the treatment of a TEMPOL, a reactive oxygen species scavenger, or TRPA1−/− mice successfully alleviated the FTE-induced p-ERK expression in the dorsal horn. The production of H2O2, a reactive oxygen species, through physical exercise contributes to angina development following I/R. Hence, our findings may be useful for understanding and treating angina following revascularisation therapy. Full article
(This article belongs to the Special Issue State-of-the-Art Molecular Pharmacology in Japan)
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11 pages, 1712 KiB  
Article
Comparison of L- and D-Amino Acids for Bacterial Imaging in Lung Infection Mouse Model
by Yuka Muranaka, Asuka Mizutani, Masato Kobayashi, Koya Nakamoto, Miki Matsue, Kodai Nishi, Kana Yamazaki, Ryuichi Nishii, Naoto Shikano, Shigefumi Okamoto and Keiichi Kawai
Int. J. Mol. Sci. 2022, 23(5), 2467; https://doi.org/10.3390/ijms23052467 - 23 Feb 2022
Cited by 5 | Viewed by 1895
Abstract
The effectiveness of L- and D-amino acids for detecting the early stage of infection in bacterial imaging was compared. We evaluated the accumulation of 3H-L-methionine (Met), 3H-D-Met, 3H-L-alanine (Ala), and 3H-D-Ala in E. coli EC-14 and HaCaT cells. Biological [...] Read more.
The effectiveness of L- and D-amino acids for detecting the early stage of infection in bacterial imaging was compared. We evaluated the accumulation of 3H-L-methionine (Met), 3H-D-Met, 3H-L-alanine (Ala), and 3H-D-Ala in E. coli EC-14 and HaCaT cells. Biological distribution was assessed in control and lung-infection-model mice with EC-14 using 3H-L- and D-Met, and 18F-FDG. A maximum accumulation of 3H-L- and D-Met, and 3H-L- and D-Ala occurred in the growth phase of EC-14 in vitro. The accumulation of 3H-L-Met and L-Ala was greater than that of 3H-D-Met and D-Ala in both EC-14 and HaCaT cells. For all radiotracers, the accumulation was greater in EC-14 than in HaCaT cells at early time points. The accumulation was identified at 5 min after injection in EC-14, whereas the accumulation gradually increased in HaCaT cells over time. There was little difference in biodistribution between 3H-L-and D-Met except in the brain. 3H-L- and D-Met were sensitive for detecting areas of infection after the spread of bacteria throughout the body, whereas 18F-FDG mainly detected primary infection areas. Therefore, 11C-L- and D-Met, radioisotopes that differ only in terms of 3H labeling, could be superior to 18F-FDG for detecting bacterial infection in lung-infection-model mice. Full article
(This article belongs to the Special Issue State-of-the-Art Molecular Pharmacology in Japan)
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