Article
Biology
Ralf Schmauder, Thomas Eick, Eckhard Schulz, Guenther Sammler, Elmar Voigt, Guenter Mayer, Holger Ginter, Guenter Ditze, Klaus Benndorf
Summary: By using a microfluidic chip-based technique, we have developed a method for studying ion currents and fluorescence signals in order to measure the kinetics of channel activation and deactivation, as well as ligand binding and unbinding. This approach allows for the rapid generation of concentration-activation relationships and activation kinetics, while minimizing the effects of interference.
COMMUNICATIONS BIOLOGY
(2023)
Article
Cell Biology
Anna Pegoraro, Elena De Marchi, Manuela Ferracin, Elisa Orioli, Michele Zanoni, Cristian Bassi, Anna Tesei, Marina Capece, Emi Dika, Massimo Negrini, Francesco Di Virgilio, Elena Adinolfi
Summary: Research has shown that the overexpression of P2X7 is closely correlated with reduced overall survival in patients with metastatic malignant melanoma. Inhibiting the P2X7 receptor in melanoma cells can effectively suppress growth, migration, and metastasis. P2X7 stimulation triggers the release of microvesicles and exosomes containing miRNA from melanoma cells, suggesting a potential mechanism for the pro-metastatic activity of P2X7.
CELL DEATH & DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Eleonore Bertin, Thomas Deluc, Kjara S. Pilch, Audrey Martinez, Johan-Till Pougnet, Evelyne Doudnikoff, Anne-Emilie Allain, Philine Bergmann, Marion Russeau, Estelle Toulme, Erwan Bezard, Friedrich Koch-Nolte, Philippe Seguela, Sabine Levi, Bruno Bontempi, Francois Georges, Sandrine S. Bertrand, Olivier Nicole, Eric Boue-Grabot
Summary: Increased surface density of neuronal P2X4 contributes to synaptic deficits, alterations in anxiety and memory functions, consistent with the implication of P2X4 in neuropsychiatric and neurodegenerative disorders. These conditional P2X4mCherryIN knock-in mice provide a new approach to explore the cell-specific roles of P2X4 in various physiological and pathological contexts.
MOLECULAR PSYCHIATRY
(2021)
Article
Oncology
Garrett Rhodes, Kristen L. Segars, Yoonjoo K. Lee, Audrey E. K. Hutcheon, Celeste B. Rich, Vickery Trinkaus-Randall
Summary: The study showed that the interaction between pannexin1 and P2X7 is altered in pretype 2 diabetic tissue, and pannexin1 plays a role in the healing response. The irregular cell morphology and reduced cell-cell communication in DiO tissue suggest the importance of pannexin1 in the coordinated movement of epithelial sheets during wound healing.
ANALYTICAL CELLULAR PATHOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Brian F. King
Summary: The P2X5 receptor, a member of the ATP-gated P2X ion-channel family, has been relatively understudied due to the belief that it is non-functional in humans and weakly functional in rats and mice. However, recent studies have shown that a small proportion of humans possess full-length P2X5 subunits and that replacing certain amino acids in rat P2X5 subunits can significantly improve their responsiveness to ATP.
PURINERGIC SIGNALLING
(2023)
Review
Pharmacology & Pharmacy
Francesco Di Virgilio, Valentina Vultaggio-Poma, Alba Clara Sarti
Summary: Ion channels, especially P2X receptors, play crucial roles in tumor development, closely related to extracellular ATP, and could be key regulators of tumor growth.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Neurosciences
Silvia Prades, Gregory Heard, Jonathan E. Gale, Tobias Engel, Robin Kopp, Annette Nicke, Katie E. Smith, Daniel J. Jagger
Summary: The P2X(7) receptors are primarily expressed by peripheral glial cells rather than afferent neurons in the auditory nerve. This finding contributes to a better understanding of the effects of ATP-dependent mechanisms on hearing loss and sensory neuropathies.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Xiaolu Lei, Junwei Zeng, Yan Yan, Xiaohong Liu
Summary: This study aimed to investigate the modulation of HCN channel activity on the expression and function of P2X2 and P2X3 receptors. The results showed that intrathecal administration of HCN channel blocker ZD7288 significantly reduced mechanical hyperalgesia and the increased expression of P2X2 and P2X3 receptors in rats with chronic constriction injury of sciatic nerve. Furthermore, it was found that the opening of HCN channels could enhance the expression and function of P2X2 and P2X3 receptors via the cAMP-PKA signaling pathway. These findings provide important insights into the mechanism of nerve injury-induced pain hypersensitivity.
NEUROCHEMICAL RESEARCH
(2022)
Review
Medicine, Research & Experimental
Ji-peng Liu, Si-cheng Liu, Shi-qi Hu, Jia-feng Lu, Chang-lei Wu, Dong-xia Hu, Wen-jun Zhang
Summary: Multiple studies have shown that P2X purinergic receptors play a crucial role in inflammation. These receptors, when activated, release inflammatory cytokines and contribute to the progression of inflammatory diseases. In an inflammatory microenvironment, cells release ATP to activate P2X receptors, leading to the activation of various intracellular signaling pathways and the release of multiple inflammatory cytokines, thereby amplifying the inflammatory response. P2X4 and P2X7 receptors are especially important in the process of inflammation, mediating the activation of microglia and different inflammatory cells, respectively, and contributing to tissue-wide inflammation. This paper discusses the role of P2X receptors in mediating inflammation and describes the effects of various antagonists on inflammation relief by targeting P2X receptors.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Pharmacology & Pharmacy
Jasmin Ballout, Rebecca Classen, Katrin Richter, Veronika Grau, Martin Diener
Summary: This study found that ionotropic P2X receptors are involved in the regulation of intestinal ion transport in rat colonic epithelia.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Chemistry, Medicinal
Allen T. Hopper, Martin Juhl, Jorrit Hornberg, Lassina Badolo, John Paul Kilburn, Annemette Thougaard, Gennady Smagin, Dekun Song, Londye Calice, Veena Menon, Elena Dale, Hong Zhang, Manuel Cajina, Megan E. Nattini, Adarsh Gandhi, Michel Grenon, Ken Jones, Tanzilya Khayrullina, Gamini Chandrasena, Christian Thomsen, Stevin H. Zorn, Robb Brodbeck, Suresh Babu Poda, Roland Staal, Thomas Moller
Summary: Lu AF27139 is a novel rodent-active and CNS-penetrant P2X7 receptor antagonist, showing high selectivity and potency against rat, mouse, and human forms of the receptors, as well as favorable pharmacokinetic properties. In vivo studies demonstrate functional CNS target engagement, while in vitro and in vivo toxicity studies show no adverse effects. It is believed that Lu AF27139 will be a valuable tool for exploring the role of the P2X7 receptor in rodent models of CNS diseases.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Waldemar Schaefer, Tobias Staehler, Carolina Pinto Espinoza, Welbeck Danquah, Jan Hendrik Knop, Bjoern Rissiek, Friedrich Haag, Friedrich Koch-Nolte
Summary: P2X7, an ion channel gated by extracellular ATP, plays important roles in inflammation and apoptosis. Polymorphisms in the P2X7 gene are common, and their frequencies vary among different human populations. Considering P2X7 variants of participants is important in designing clinical trials targeting P2X7.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Yeting Zeng, Huoqing Luo, Zilong Gao, Xiaona Zhu, Yinbo Shen, Yulong Li, Ji Hu, Jiajun Yang
Summary: The study indicates that the analgesic effect of morphine is related to the reduction of purinergic signaling in the prefrontal cortex, and inhibiting P2X7R in the mPFC can mimic morphine analgesia. In morphine-tolerant mice, pretreatment with P2X4R or P2X7R antagonists in the mPFC enhances the analgesic effect of morphine.
Article
Multidisciplinary Sciences
Carlos Barrera-Avalos, Pedro Briceno, Daniel Valdes, Monica Imarai, Elias Leiva-Salcedo, Leonel E. Rojo, Luis A. Milla, Juan Pablo Huidobro-Toro, Claudia Robles-Planells, Alejandro Escobar, Francesco Di Virgilio, Gabriel Moron, Daniela Sauma, Claudio Acuna-Castillo
Summary: The research highlights the significance of cross-dressing as a non-conventional antigen presentation mechanism, and demonstrates the crucial role of the P2X7 receptor in inducing cross-dressing between apoptotic cells and bone marrow dendritic cells.
Review
Pharmacology & Pharmacy
Marie-Louise T. Monaghan, Matthew A. Bailey, Robert J. Unwin
Summary: Historically, renal vascular and tubular function has been mainly controlled through neural and endocrine regulation. However, it is now acknowledged that complex humoral control systems exist within the kidney, complementing neuroendocrine regulation by fine-tuning renal function in response to rapid changes. The extracellular nucleotide/P2 receptor system plays a central role in intrinsic regulatory feedback loops within the kidney, contributing to the understanding and potential treatment of kidney disease.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Critical Care Medicine
Christine H. Meyer-Friessem, Nathalie M. Malewicz, Sabrina Rath, Melanie Ebel, Miriam Kaisler, Martin Tegenthoff, Thomas A. Schildhauer, Esther M. Pogatzki-Zahn, Christoph Maier, Peter K. Zahn
Summary: ICUAW symptoms are disturbingly common in the majority of long-term survivors, impairing quality of life significantly, yet only a small number of patients have been diagnosed with ICUAW.
JOURNAL OF INTENSIVE CARE MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Ye Hyung Lee, Eunju Im, Minju Hyun, Joongkyu Park, Kwang Chul Chung
Summary: DYRK1A protein is associated with developmental symptoms of DS and AD, and the interaction with PPM1B leads to dephosphorylation of tau protein, inhibiting toxic aggregation, thus providing a potential mechanism for regulating neurodegeneration in AD.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biology
Amanda Klein, Hans Jurgen Solinski, Nathalie M. Malewicz, Hada Fong-ha Ieong, Elizabeth Sypek, Steven G. Shimada, Timothy Hartke, Matthew Wooten, Gang Wu, Xinzhong Dong, Mark A. Hoon, Robert H. LaMotte, Matthias Ringkamp
Summary: In humans, certain neurons in the dorsal root ganglion express receptors for pruritogens such as ALA and BAM8-22, whereas in nonhuman primates, specific C-fiber nociceptors are preferentially activated by these pruritogens. Additionally, when pruritogens are administered in combination, human volunteers report itch and nociceptive sensations similar to those induced by a single pruritogen. These findings suggest differences in pruriceptive processing between primates and rodents, and challenge the spatial contrast theory of coding of itch and pain.
Article
Medicine, General & Internal
Christine H. Meyer-Friessem, Sabeth Huesken, Miriam Kaisler, Nathalie M. Malewicz, Peter K. Zahn, Andreas Baumann
Summary: In cardiac anesthesia, the use of isoflurane with dual antiemetic prophylaxis results in a lower incidence of PONV compared to TIVA, but high-risk patients still have a higher rate of PONV as predicted. The addition of a third antiemetic prophylactic drug may be necessary for high-risk patients receiving isoflurane.
CURRENT MEDICAL RESEARCH AND OPINION
(2021)
Review
Neurosciences
Miwako Yamasaki, Atsu Aiba, Masanobu Kano, Masahiko Watanabe
Summary: The Purkinje cells in the cerebellar cortex play crucial roles in controlling cerebellar functions through triggering signaling pathways via mGluR1. Studies suggest that mGluR1 and its related signaling molecules form microdomains that are essential for physiological functions. Altered mGluR1 signaling is associated with cerebellar dysfunction such as ataxias in both human patients and mouse models.
Article
Neurosciences
Ken Matsuura, Shizuka Kobayashi, Kohtarou Konno, Miwako Yamasaki, Takahiro Horiuchi, Takao Senda, Tomoatsu Hayashi, Kiyotoshi Satoh, Fumiko Arima-Yoshida, Kei Iwasaki, Lumi Negishi, Naomi Yasui-Shimizu, Kazuyoshi Kohu, Shigenori Kawahara, Yutaka Kirino, Tsutomu Nakamura, Masahiko Watanabe, Tadashi Yamamoto, Toshiya Manabe, Tetsu Akiyama
Summary: The study reveals that SIPA1L1 is mainly localized to submembranous regions in neurons, and its deficiency may be associated with neuropsychiatric disorders related to dysregulated GPCR signaling.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Neurosciences
Czarina Ramos, Stefano Lutzu, Miwako Yamasaki, Yuchio Yanagawa, Kenji Sakimura, Susumu Tomita, Masahiko Watanabe, Pablo E. Castillo
Summary: This study provides the first direct evidence of functional extrasynaptic kainate receptors (KARs) on mossy cells (MCs) in the hippocampus. These KARs are mainly located extrasynaptically and play a critical role in the activity of MCs. Increases in ambient glutamate can activate the KARs on MCs.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Cell & Tissue Engineering
Yuka Kasahara, Daiki Masukawa, Kenta Kobayashi, Miwako Yamasaki, Masahiko Watanabe, Yoshio Goshima
Summary: Neurogenesis in the hippocampus is regulated by L-DOPA and its receptor GPR143 independently of dopamine. Low concentrations of L-DOPA promote neurogenesis, and its effect is abolished in GPR143 gene-deficient mice. Decreased neurogenesis and exacerbated depression-like behavior are observed in adult GPR143 gene-deficient mice, but can be attenuated by replenishment of GPR143 in the hippocampus.
Article
Dermatology
N. M. Malewicz, H. F. -h Ieong, S. Oeck, N. Kumowski, Z. Zhang, S. G. Shimada, R. H. LaMotte
Summary: This study found that ficin can induce itch and nociceptive sensations in humans and mice, and the effects in mice are dose-dependent. This finding suggests that ficin may be useful for studying the neural mechanisms of pruritic and nociceptive effects of cysteine proteases.
JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY
(2022)
Article
Rheumatology
Nobuya Abe, Masato Tarumi, Yuichiro Fujieda, Nobuhiko Takahashi, Kohei Karino, Mona Uchida, Michihito Kono, Yuki Tanaka, Rie Hasebe, Masaru Kato, Olga Amengual, Yoshiyuki Arinuma, Kenji Oku, Wakiro Sato, Khin Khin Tha, Miwako Yamasaki, Masahiko Watanabe, Tatsuya Atsumi, Masaaki Murakami
Summary: The study investigates the effects of stress on the pathophysiology of neuropsychiatric lupus (NPSLE) in systemic lupus erythematosus (SLE) using lupus-prone mice and patient data.
ANNALS OF THE RHEUMATIC DISEASES
(2022)
Article
Multidisciplinary Sciences
Ching-Pu Chang, Kohei Otomo, Yuichi Kozawa, Hirokazu Ishii, Miwako Yamasaki, Masahiko Watanabe, Shunichi Sato, Ryosuke Enoki, Tomomi Nemoto
Summary: Researchers have developed an easy-to-use light-needle creating device for conventional two-photon microscopy systems. The device allows for single scanning excitation of fluorophores in specimens with a thickness over 200μm, enabling three-dimensional monitoring of biological tissues and their network activities.
SCIENTIFIC REPORTS
(2022)
Article
Neurosciences
Adrian J. Duszkiewicz, Janine I. Rossato, Andrea Moreno, Tomonori Takeuchi, Miwako Yamasaki, Lisa Genzel, Patrick Spooner, Santiago Canals, Richard G. M. Morris
Summary: The hippocampus plays a critical role in mammalian spatial navigation, with its firing sequences during sleep or immobility representing past trajectories. A recent study showed that these sequences can also map onto new paths to a goal. However, inactivating the dorsal and intermediate hippocampus had minimal effects on the same spatial navigation task, raising doubts about the causal role of prospective replay sequences. Findings from a watermaze task indicate that muscimol-induced inactivation severely impaired hippocampal-dependent episodic-like spatial memory.
Article
Multidisciplinary Sciences
Kohtarou Konno, Miwako Yamasaki, Taisuke Miyazaki, Masahiko Watanabe
Summary: The gold-standard fixative for immunohistochemistry is 4% formaldehyde; however, it limits antibody access to buried target molecules. To solve this problem, we used glyoxal as a fixative, which greatly improved antibody penetration, uncovering signals for buried molecules. Glyoxal also enhanced immunosignals of most other molecules, including the controversial synaptic adhesion molecule Neuroligin 1.
Article
Multidisciplinary Sciences
Hitomi Sasamori, Toshiaki Asakura, Chiaki Sugiura, Youcef Bouchekioua, Naoya Nishitani, Masaaki Sato, Takayuki Yoshida, Miwako Yamasaki, Akira Terao, Masahiko Watanabe, Yu Ohmura, Mitsuhiro Yoshioka
Summary: This study examined the role of dopamine D-5 receptors in impulse control and found that they are not necessary for impulse control. The results highlight the importance of time series analysis and detailed analysis of the learning process in understanding the behavioral functions of D-5 receptors.
SCIENTIFIC REPORTS
(2022)
Article
Clinical Neurology
Kouichi Hashimoto, Yosuke Yamawaki, Kenji Yamaoka, Takayuki Yoshida, Kana Okada, Wanqin Tan, Miwako Yamasaki, Yoshiko Matsumoto-Makidono, Reika Kubo, Hisako Nakayama, Tsutomu Kataoka, Takashi Kanematsu, Masahiko Watanabe, Yasumasa Okamoto, Shigeru Morinobu, Hidenori Aizawa, Shigeto Yamawaki
Summary: Research found that the depolarization-induced spike firing of serotonin neurons was attenuated in rats showing learned helplessness, likely due to the regulation of K+ channels. Drugs targeting Kv1 channels could reverse this firing attenuation, serving as a potential target for controlling the activity of serotonin neurons.
BRAIN COMMUNICATIONS
(2021)
