Review
Pharmacology & Pharmacy
Shanu Jain, Kenneth A. Jacobson
Summary: Purinergic signaling, originally proposed by Geoffrey Burnstock, plays a crucial role in modulating pathways in various physiological systems. Adenosine receptors and P2 nucleotide receptors are involved in metabolic disorders, affecting specific cell types like adipocytes, skeletal muscle, liver cells, and immune cells. Selective ligands for adenosine and P2 receptors may have therapeutic potential for diabetes and obesity, but conflicting conclusions exist in drug discovery related to this topic.
BIOCHEMICAL PHARMACOLOGY
(2021)
Review
Pharmacology & Pharmacy
Charles Kennedy
Summary: Extracellular purine and pyrimidine nucleotides produce pharmacological effects through P2 receptors, which are divided into P2X and P2Y families based on pharmacological criteria. Progress in cloning and high resolution imaging has provided insights into how agonists and antagonists bind to receptors, leading to changes in receptor conformation and activity. This has led to the development of subtype-selective agonists and antagonists, some of which are now in clinical use, showcasing the foresight and drive of Geoff Burnstock in advancing the field.
BIOCHEMICAL PHARMACOLOGY
(2021)
Review
Pharmacology & Pharmacy
Alexei Verkhratsky
Summary: Purines and pyrimidines are essential molecules for genetic code and bioenergetics. Through evolution, purines have been associated with damage-related extracellular signaling, while plants have developed a sophisticated purinergic signaling system. In vertebrates, the purinergic signaling system operates universally without anatomical or functional segregation.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Neurosciences
Paula Mut-Arbona, Beata Sperlagh
Summary: The purinergic pathway is involved in both pro-inflammatory and anti-inflammatory responses, and the breakdown of ATP is essential in maintaining its balance. ATP is considered a clear indicator of cell damage and pathological conditions when released during tissue damage, inflammation, or hypoxia. This review focuses on the role of P2 receptor-mediated purinergic signaling in normal and pathological brain development, particularly in neurodevelopmental psychiatric disorders. The review emphasizes the timedependent dynamic changes in the purinome and its involvement in shaping the normal and aberrant patterns of central nervous system development and diseases over one's lifespan.
Review
Biochemistry & Molecular Biology
Srdjan M. M. Vlajkovic, Peter R. R. Thorne
Summary: The mammalian cochlea, as the sensory organ for hearing, is regulated by ATP release and adenosine signaling, triggering various physiological responses and playing important roles in cochlear development, homeostasis, and sensory transduction. Understanding these mechanisms may provide therapeutic strategies for cochlear rescue and prevention of hearing loss.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Sun-Hee Woo, Tran Nguyet Trinh
Summary: ATP serves as a major energy source in mammalian cells but also acts as an extracellular chemical messenger through P2 purinergic receptors. Different types of cells release ATP, including neurons, endothelial cells, and muscle cells. Studies have shown the distribution and roles of P2 receptor subtypes in cardiac cells under physiological and pathological conditions, with specific genetic alterations and pharmacological approaches revealing distinct functions of P2 receptors in the heart.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Kenneth A. Jacobson, Adriaan P. IJzerman, Christa E. Mueller
Summary: This review paper explores the historical origins of P2 receptors and adenosine receptor ligands, emphasizing the versatility of common chemical scaffolds for multiple receptor targets. By analyzing structure activity relationships, selective receptor subtype targeting can be achieved, leading to potential therapeutic applications in various diseases.
BIOCHEMICAL PHARMACOLOGY
(2021)
Review
Pharmacology & Pharmacy
Aleksandra Szopa, Katarzyna Socala, Anna Serefko, Urszula Doboszewska, Andrzej Wrobel, Ewa Poleszak, Piotr Wlaz
Summary: Purinergic signaling plays a significant role in depression, with studies suggesting altered adenosine metabolism in depressed patients may serve as a disease biomarker. Research also indicates that manipulation of P1 or P2 receptors, along with selective or nonselective ligands, can impact the development and progression of depression.
PHARMACOLOGY & THERAPEUTICS
(2021)
Review
Neurosciences
Peter Illes, Henning Ulrich, Jiang-Fan Chen, Yong Tang
Summary: Purinergic receptors of the ATP/ADP, UTP/UDP and adenosine-sensitive classes play a broad role in cognitive processes, both in normal and disease conditions. Neurodegenerative diseases are associated with the release of high concentrations of ATP, which is enzymatically degraded to adenosine. Activation of P2X7 and A2AR receptors on various protein aggregates contributes to the primary injury, and small molecular antagonists show promise in preventing or mitigating this damage in animal models. Purinergic receptors are also implicated in psychiatric diseases, suggesting their potential as therapeutic targets for cognitive deterioration.
NEUROBIOLOGY OF DISEASE
(2023)
Review
Pharmacology & Pharmacy
Yuemei Wang, Yuanbing Zhu, Junmeng Wang, Longcong Dong, Shuqing Liu, Sihui Li, Qiaofeng Wu
Summary: This review summarizes the evidence that purinergic signaling plays a role in regulating blood-brain barrier (BBB) permeability. Various cell types, including endothelial cells, pericytes, neurons, astrocytes, microglia, and oligodendrocytes, contribute to maintaining the integrity of the BBB. Purinergic receptors such as P2Y and A receptors, as well as nucleotidases, are expressed on BBB cells and affect BBB permeability. Selective antagonists of P2Y receptors attenuate BBB damage, while agonists of A receptors protect BBB integrity. Modulating purinergic signaling could be a potential strategy for delivering therapeutic drugs to the central nervous system and restoring CNS homeostasis.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Endocrinology & Metabolism
Nour Mesto, Jamileh Movassat, Cecile Tourrel-Cuzin
Summary: This article reviews the role of P2-type purinergic signaling in the regulation of pancreatic beta-cell functional plasticity, which could be a promising novel therapeutic approach for the treatment of type 2 diabetes.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Janielle P. Maynard, Karen S. Sfanos
Summary: P2 purinergic receptors play a crucial role in the normal function of the kidney, bladder, and prostate, as well as in various urologic disorders. Dysregulation of these receptors is associated with disease initiation and progression. Additionally, these receptors are overexpressed in urologic cancers and have potential as therapeutic targets. Exploring the role of P2 purinergic receptors in urologic diseases can provide new mechanistic insights and potential treatment options.
PURINERGIC SIGNALLING
(2022)
Review
Biochemistry & Molecular Biology
Muhammad Aslam, Dursun Gunduz, Christian Troidl, Jacqueline Heger, Christian W. Hamm, Rainer Schulz
Summary: This review discusses the influence of activation of various purinergic receptors and downstream signaling pathways on vascular permeability during pathological conditions, noting that the effects may depend on the type and prevalence of activated receptors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
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)
Review
Oncology
Jasmeet Kaur, Sanchit Dora
Summary: Cancer is a complex disease with diverse characteristics, and there is a need to discover new therapeutic targets to improve treatment outcomes.
FRONTIERS IN ONCOLOGY
(2023)
Review
Pharmacology & Pharmacy
Charles Kennedy
Summary: Extracellular purine and pyrimidine nucleotides produce pharmacological effects through P2 receptors, which are divided into P2X and P2Y families based on pharmacological criteria. Progress in cloning and high resolution imaging has provided insights into how agonists and antagonists bind to receptors, leading to changes in receptor conformation and activity. This has led to the development of subtype-selective agonists and antagonists, some of which are now in clinical use, showcasing the foresight and drive of Geoff Burnstock in advancing the field.
BIOCHEMICAL PHARMACOLOGY
(2021)
Review
Pharmacology & Pharmacy
Peter Illes, Christa E. Mueller, Kenneth A. Jacobson, Thomas Grutter, Annette Nicke, Samuel J. Fountain, Charles Kennedy, Gunther Schmalzing, Michael F. Jarvis, Stanko S. Stojilkovic, Brian F. King, Francesco Di Virgilio
Summary: P2X receptors are cationic channels consisting of seven different subunits, with researchers having determined their structure and function. In addition, primitive ligand-gated counterparts related to P2X receptors have been cloned, and various selective antagonists have been discovered.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Gastroenterology & Hepatology
Sara Traserra, Claudia Barber, Jane Maclnnes, Lucia Relea, Lewis C. MacPherson, Margaret R. Cunningham, Patri Vergara, Anna Accarino, Charles Kennedy, Marcel Jimenez
Summary: BPTU affects purinergic neurotransmission in pig and human gastrointestinal tissues by inhibiting P2Y(1) receptors. However, the concentration needed for effectiveness is higher in pig tissue compared to human colonic tissue.
NEUROGASTROENTEROLOGY AND MOTILITY
(2021)
Article
Biochemistry & Molecular Biology
Charles Kennedy
Summary: P2 receptors are present in various tissues and cell types in the human body, mediating physiological and pharmacological actions of extracellular nucleotides. Through molecular cloning and structural studies, the mechanisms of P2X and P2Y receptors have been better understood.
PURINERGIC SIGNALLING
(2021)
Article
Chemistry, Medicinal
Ngamrayu Ngamdokmai, Tamkeen Urooj Paracha, Neti Waranuch, Krongkarn Chootip, Wudtichai Wisuitiprot, Nungruthai Suphrom, Kamonlak Insumrong, Kornkanok Ingkaninan
Summary: The study found that eight essential oils, two water extracts, and nine monoterpenoid constituents demonstrated inhibitory effects on lipid accumulation in adipocytes, with the mixed oil showing vasorelaxation activity. These findings suggest that these components may be responsible for the anti-cellulite effects of the herbal compress.
Article
Biochemistry & Molecular Biology
Genet Minale, Tongchai Saesong, Prapapan Temkitthawon, Neti Waranuch, Nitra Nuengchamnong, Krongkarn Chootip, Natakorn Kamkaew, Teeraporn Kongbangkerd, Jinutda Engsuwan, Kornkanok Ingkaninan
Summary: Through LC-MS metabolomics approach, altered metabolites in the plasma, urine, and feces of healthy volunteers after consuming Brahmi essence for 12 weeks were characterized, with identified metabolites mainly including amino acids, acylcarnitine, and phospholipids. The pathways of aminoacyl-tRNA, aromatic amino acids, and branched-chain amino acids biosynthesis were found to be associated with the effect of Brahmi essence on memory speed.
Article
Chemistry, Medicinal
Ngamrayu Ngamdokmai, Kornkanok Ingkaninan, Nattiya Chaichamnong, Krongkarn Chootip, Nitra Neungchamnong, Neti Waranuch
Summary: The study successfully developed an anti-cellulite emgel with herbal ingredients, and evaluated its stability over a 31-month period. The formulated dosage form showed consistent caffeine content and stable monoterpenes for up to 2 months at 50 degrees Celsius.
Article
Chemistry, Medicinal
Ngamrayu Ngamdokmai, Neti Waranuch, Krongkarn Chootip, Katechan Jampachaisri, C. Norman Scholfield, Kornkanok Ingkaninan
Summary: A herbal 'emgel' containing extracts of a traditional Thai herbal compress was tested on women with severe cellulite, showing improvement in the appearance of cellulite and safety in use. Further studies on active constituents and mechanisms of action are needed for future exploration.
Article
Integrative & Complementary Medicine
Anjaree Inchan, Thanika Pathomwichaiwat, Tippaporn Bualeong, Sasipong Tipratchadaporn, Krongkarn Chootip
Summary: The study evaluated the effects of Yahom Navakot (YN), a traditional Thai medicine, on orthostatic hypotension (OH) in rats. The results showed that YN can alleviate OH symptoms by stimulating the heart and blood vessels via sympathetic activation, supporting its traditional use for OH prevention.
JOURNAL OF TRADITIONAL AND COMPLEMENTARY MEDICINE
(2022)
Article
Integrative & Complementary Medicine
Suriya Chaiwong, Usana Chatturong, Rachanee Chanasong, Watcharakorn Deetud, Kittiwoot To-on, Supaporn Puntheeranurak, Ekarin Chulikorn, Tanwarat Kajsongkram, Veerada Raksanoh, Kroekkiat Chinda, Nanteetip Limpeanchob, Kanittaporn Trisat, Julintorn Somran, Nitra Nuengchamnong, Piya Prajumwong, Krongkarn Chootip
Summary: The study shows that freshly dried mulberry fruits have a positive effect on preventing metabolic and cardiovascular pathologies caused by high-fat diet. Mulberry fruits can reduce risk factors of hyperlipidemia and improve liver pathology, helping to prevent arterial and cardiac wall thickening, weight gain, and fat accumulation.
JOURNAL OF TRADITIONAL AND COMPLEMENTARY MEDICINE
(2021)
Article
Neurosciences
Charles Kennedy
Summary: Geoff Burnstock's scientific legacy includes the identification of ATP as a neurotransmitter in the gut, the discovery of a large family of receptors, and the demonstration of ATP's role as an excitatory cotransmitter in autonomic nerves. The potential therapeutic application of cotransmission in treating dysfunctional bladder disorders is a promising area of research.
AUTONOMIC NEUROSCIENCE-BASIC & CLINICAL
(2021)
Editorial Material
Biochemistry & Molecular Biology
Charles Kennedy
PURINERGIC SIGNALLING
(2021)
Article
Multidisciplinary Sciences
Kittiwoot To-on, Usana Chatturong, Teerapap Panklai, Iyapa Palang, Anjaree Inchan, Sutthinee Wisutthathum, Tamkeen Urooj Paracha, Phapada Apaikawee, Krongkarn Chootip
Summary: This study explores the use of intrapulmonary artery and vascular smooth muscle cells isolated from rat lungs to study the mechanisms of vasoconstriction and vasorelaxation. The isolated cells allow for assessment of vascular responses without the influence of extrinsic factors, providing a valuable model for studying vascular physiology/pathophysiology.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2022)
Article
Biochemistry & Molecular Biology
Markie O. Dales, Callum Mitchell, Alison M. Gurney, Robert M. Drummond, Charles Kennedy
Summary: This study investigated the roles of individual P2Y receptor subtypes in nucleotide-induced pulmonary vasodilation and vasoconstriction. The results showed that UTP causes pulmonary vasodilation via P2Y(2) receptors, UDP acts on P2Y(6) receptors, and ADP acts on P2Y(1) receptors. The mechanism of ATP-induced vasodilation remains unclear.
PURINERGIC SIGNALLING
(2022)
Article
Biochemistry & Molecular Biology
Teerapap Panklai, Nungruthai Suphrom, Prapapan Temkitthawon, Perle Totoson, Krongkarn Chootip, Xiao-Liang Yang, Hui-Ming Ge, Zhu-Jun Yao, Nattiya Chaichamnong, Kornkanok Ingkaninan, Corine Girard
Summary: The objective of this study was to investigate the effect of plant extracts from Nelumbonaceae and Nymphaeaceae on PDE5 and arginase, and to identify the compounds responsible for these activities.