Article
Multidisciplinary Sciences
Elle C. Roberson, Ngan Kim Tran, Anushka N. Godambe, Harrison Mark, Michelle Nguimtsop, Trinity Rust, Elizabeth Ung, LeCaine J. Barker, Rebecca D. Fitch, John B. Wallingford
Summary: Decades of research have shown that the mammalian estrous cycle is regulated by cycling steroid hormones. However, the signaling mechanisms connecting hormonal action and the physical changes in the uterus during the cycle are still unclear. In this study, gene expression during all stages of the mouse estrous cycle was analyzed, revealing that several genetic programs responsible for tissue morphogenesis in developing embryos display cyclical patterns of expression. Furthermore, it was found that most of the genes involved in the Hedgehog signaling pathway are transcribed cyclically in the uterus. Disruption of the Hedgehog receptor smoothened not only affects the normal thickening of the endometrial lining but also induces abnormal deformation of the uterine smooth muscle. These findings provide insights into the mechanisms underlying normal uterine remodeling and cyclical gene expression.
Review
Biochemistry & Molecular Biology
Iain L. O. Buxton, Hazik Asif, Scott D. D. Barnett
Summary: Preterm labor leading to preterm birth is currently not preventable. Beta 2 agonists and nitric oxide, which are effective in relaxing smooth muscles, have been ineffective in preventing preterm birth. However, recent studies suggest that the repurposing of approved medication, such as mirabegron, may advance the prevention of preterm birth.
Review
Physiology
Susan Wray, Clodagh Prendergast, Sarah Arrowsmith
Summary: This study explores the mechanisms of calcium-activated chloride channels in smooth muscle tissues and the differences in their activation and regulation in different types of smooth muscles. The findings suggest that the expression and functional importance of CaCC vary in different smooth muscle tissues, with more complexity in activation and regulation observed in vascular smooth muscles.
FRONTIERS IN PHYSIOLOGY
(2021)
Review
Cell Biology
Liana Arceri, Thanh Khoa Nguyen, Shannon Gibson, Sophia Baker, Rebecca A. A. Wingert
Summary: Endocannabinoid signaling plays crucial roles in human physiology in the function of multiple systems, including the kidneys. CB1 is the more prominent receptor within the kidney and its activity contributes to both diabetic and non-diabetic chronic kidney disease. Recent reports suggest that synthetic cannabinoid use can lead to acute kidney injury. Understanding the endocannabinoid system and its impact on kidney health and diseases can provide new insights into treatment methods.
Article
Biochemistry & Molecular Biology
Chih-Wei Chiu, Cheng-Ying Hsieh, Chih-Hao Yang, Jie-Heng Tsai, Shih-Yi Huang, Joen-Rong Sheu
Summary: Yohimbine (YOH) inhibits the proliferation and migration of vascular smooth muscle cells (VSMCs) stimulated by PDGF-BB through downregulating the α2B-adrenergic receptor-independent PLC gamma 1 pathway, and reduces neointimal formation in atherosclerosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Carla Ramon-Duaso, Ana Rocio Conde-Moro, Arnau Busquets-Garcia
Summary: In neuroscience, innovative and advanced technical accomplishments are crucial for understanding brain functioning. The discovery of functional presence of type-1 cannabinoid receptors in astroglial cells has revealed their important role in behavioral control.
Article
Pharmacology & Pharmacy
Melissa L. Kozakiewicz, Jie Zhang, Sandra Leone-Kabler, Liliya M. Yamaleyeva, Anna G. McDonald, Brian C. Brost, Allyn C. Howlett
Summary: This study aimed to investigate the role of the endocannabinoid system in labor, and found that the protein abundance of CB1 cannabinoid receptor was significantly lower in uterine tissue exposed to labor, supporting the involvement of this system in parturition. These findings contribute to the understanding of the importance of the endocannabinoid system in successful reproduction and highlight the need for further research in this area.
CANNABIS AND CANNABINOID RESEARCH
(2022)
Article
Endocrinology & Metabolism
Luciana Mateus Goncalves, Joana Almaca
Summary: The study utilized pancreas slices from non-diabetic human donors to investigate the function of human islet blood vessels, revealing the vascular responses to vasoactive stimuli and the critical role of mural cells in regulating blood perfusion in islets. The findings highlight the differences between human and rodent islet microvasculature and emphasize the importance of understanding these alterations in disease progression.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Roman C. Sarott, Alexander E. G. Viray, Patrick Pfaff, Anastasiia Sadybekov, Gabriela Rajic, Vsevolod Katritch, Erick M. Carreira, James A. Frank
Summary: CB2 receptor is a promising target for treating neuroinflammation and other diseases, but the lack of understanding of its complex signaling complicates therapeutic exploitation. A study demonstrates how the CB2 agonist HU308 affects cytosolic Ca2+ levels in cells and tissues, and shows the utility of chemical photoswitches for real-time control and monitoring of CB2 signaling.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Peripheral Vascular Disease
Lin-Na Wang, Meng-Dan Xing, Wan-Ting Qu, Cong-Bei Wang, Zhi-Qiang Liu, Jing Han, Wei Ren, Yan-Ning Qiao
Summary: The study suggests that vascular smooth muscle CB1 receptors play a key role in mediating the vasodilation effects of cannabinoids, particularly in ischemic conditions such as stroke where they exert a protective function.
MICROVASCULAR RESEARCH
(2022)
Review
Critical Care Medicine
Mariane C. G. Leite-Avalca, Aleksander Zampronio, Christian Lehmann
Summary: Sepsis is a life-threatening condition caused by dysregulated host response to infection, with no definitive treatment available. Research on the endocannabinoid system, specifically the role of CB1 and CB2 receptors in sepsis pathophysiology, may provide insights for new therapeutic strategies. Understanding the modulation of host immune response by CB1 and CB2 in sepsis could contribute to improving outcomes for patients.
Article
Multidisciplinary Sciences
Alex Straiker, Michaela Dvorakova, Taryn Bosquez-Berger, Jaroslav Blahos, Ken Mackie
Summary: Autaptic hippocampal neurons are a simple model for studying neurotransmission and cannabinoid signaling. Through our research, we have discovered interesting negative findings in these neurons, which we hope will benefit other laboratories and lead to discussions on their relevance and significance.
SCIENTIFIC REPORTS
(2023)
Article
Pharmacology & Pharmacy
Christina Wenglen, Isak Demirel, Anna Göthlin Eremo, Magnus Grenegard, Geena Paramel
Summary: Vascular smooth muscle cells (VSMCs) play a crucial role in intimal thickening and atherosclerosis progression. This study identified the expression of the 5-HT2B receptor in human atherosclerotic lesions and its positive correlation with VSMC markers. Additionally, a selective inhibitor of the 5-HT2B receptor was found to effectively inhibit TGF131-induced collagen and CTGF production through blocking the phospho-Smad2-mediated downstream signaling. This HTR2B/TGF-131/Phospho-Smad2 pathway is critical for VSMC differentiation regulation, suggesting the 5-HT2B receptor as a potential therapeutic target for limiting TGF-131-induced VSMC differentiation.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Cell Biology
Jin Niu, Chen Wu, Min Zhang, Zhen Yang, Zhenhua Liu, Feng Fu, Jun Li, Na Feng, Xiaoming Gu, Shumiao Zhang, Yali Liu, Rong Fan, Juan Li, Jianming Pei
Summary: In this study, it was found that the selective kappa-opioid receptor agonist U50,488H can inhibit calcification of rat vascular smooth muscle cells (VSMCs) by reducing PFKFB3 expression and lactate content. These findings suggest a potential drug target and strategy for the clinical treatment of vascular calcification.
Article
Cell Biology
Rolando A. Cuevas, Ryan Wong, Pouya Joolharzadeh, William J. Moorhead III, Claire C. Chu, Jack Callahan, Alex Crane, Camille K. Boufford, Angelina M. Parise, Aneesha Parwal, Parya Behzadi, Cynthia St. Hilaire
Summary: Arterial calcification due to deficiency of CD73 (ACDC) is a rare genetic disease caused by a loss-of-function mutation in the NT5E gene encoding the ecto-5'-nucleotidase (cluster of differentiation 73, CD73) enzyme. Patients with ACDC develop vessel arteriomegaly, tortuosity, and vascular calcification in their lower extremity arteries. Our study investigates whether CD73-derived adenosine modifies TGF beta signaling in vascular smooth muscle cells (SMCs) and identifies a novel link between adenosine and TGF beta signaling, where adenosine signaling via the A2b adenosine receptor attenuates TGF beta signal-ing to regulate SMC homeostasis.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2023)
Article
Pharmacology & Pharmacy
Khaled Alhosaini, Omar Bahattab, Heider Qassam, R. A. John Challiss, Gary B. Willars
MOLECULAR PHARMACOLOGY
(2018)
Article
Pharmacology & Pharmacy
Richard D. Rainbow, Sean Brennan, Robert Jackson, Alison J. Beech, Amal Bengreed, Helen Waldschmidt, John J. G. Tesmer, R. A. John Challiss, Jonathon M. Willets
MOLECULAR PHARMACOLOGY
(2018)
Article
Biochemistry & Molecular Biology
Susan W. Robinson, Julie-Myrtille Bourgognon, Jereme G. Spiers, Carlo Breda, Susanna Campesan, Adrian Butcher, Giovanna R. Mallucci, David Dinsdale, Nobuhiro Morone, Raj Mistry, Tim M. Smith, Maria Guerra-Martin, R. A. John Challiss, Flaviano Giorgini, Joern R. Steinert
Review
Anesthesiology
Salim Kadhim, John McDonald, David G. Lambert
JOURNAL OF ANESTHESIA
(2018)
Editorial Material
Anesthesiology
G. L. Ackland, H. F. Galley, B. Shelley, D. G. Lambert
BRITISH JOURNAL OF ANAESTHESIA
(2019)
Article
Biochemistry & Molecular Biology
Sophie J. Bradley, Colin Molloy, Paulina Valuskova, Louis Dwomoh, Miriam Scarpa, Mario Rossi, Lisa Finlayson, Kjell A. Svensson, Eyassu Chernet, Vanessa N. Barth, Karolina Gherbi, David A. Sykes, Caroline A. Wilson, Rajendra Mistry, Patrick M. Sexton, Arthur Christopoulos, Adrian J. Mogg, Elizabeth M. Rosethorne, Shuzo Sakata, R. A. John Challiss, Lisa M. Broad, Andrew B. Tobin
NATURE CHEMICAL BIOLOGY
(2020)
Article
Pharmacology & Pharmacy
Xianguo Jiang, John Challiss, Paul Glynn
BIOCHEMICAL PHARMACOLOGY
(2020)
Review
Biochemistry & Molecular Biology
Joaquim Azevedo Neto, Anna Costanzini, Roberto De Giorgio, David G. Lambert, Chiara Ruzza, Girolamo Calo
Article
Biochemistry & Molecular Biology
Justyna Piekielna-Ciesielska, Roberto Artali, Ammar A. H. Azzam, David G. Lambert, Alicja Kluczyk, Luca Gentilucci, Anna Janecka
Summary: This study investigates biased agonism at opioid receptors by analyzing the structural features and biased characteristics of two cyclopeptides in complex with MOP through experiments and simulations.
Review
Pharmacology & Pharmacy
Ammar A. H. Azzam, David G. Lambert
Summary: Oliceridine, a selective MOP receptor agonist with a bias towards G-proteins, has shown good analgesic efficacy and improved respiratory safety profile in clinical trials, making it an important addition to the management of acute pain. It acts as a partial agonist and has a shorter duration of action compared to morphine. Oliceridine has been approved by the FDA.
EXPERT OPINION ON DRUG DISCOVERY
(2022)
Article
Multidisciplinary Sciences
M. F. Bird, J. McDonald, B. Horley, J. P. O'Doherty, B. Fraser, C. L. Gibson, R. Guerrini, G. Calo, D. G. Lambert
Summary: This study demonstrates the interaction between MOP and NOP, which reduces the responsiveness of MOP activation and decreases side effects. We used different methods, such as bivalent ligands and fluorescent probes, to investigate the MOP-NOP interaction, and the results showed their presence in both recombinant and native tissue.
Article
Biochemistry & Molecular Biology
Karol Wtorek, Alessia Ghidini, Luca Gentilucci, Anna Adamska-Bartlomiejczyk, Justyna Piekielna-Ciesielska, Chiara Ruzza, Chiara Sturaro, Girolamo Calo, Stefano Pieretti, Alicja Kluczyk, John McDonald, David G. Lambert, Anna Janecka
Summary: Recently, two novel chimeric peptides, KW-495 and KW-496, were developed as mixed opioid/NOP agonists. KW-495 showed low nM affinity as a mixed MOP/NOP agonist, while KW-496 became a dual KOP/MOP agonist. In in vivo experiments, KW-495 exhibited antinociceptive effects in mice and was sensitive to opioid receptor antagonists.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Mark F. Bird, Barbara Gallacher-Horley, John McDonald, David G. McVey, Fatin Al-Janabi, Remo Guerrini, Girolamo Calo, Shu Ye, Jonathan P. Thompson, David G. Lambert
Summary: Sepsis is a dysregulated host response to infection that can cause widespread effects on other organs. The study found that N/OFQ receptors are expressed on immune cells and vascular endothelial cells, and LPS/PepG treatment increases functional expression of NOP receptors in vascular endothelium. These findings may contribute to our understanding of the hypotensive response in sepsis and provide new therapeutic targets for its treatment.
Article
Pharmacology & Pharmacy
Mark F. Bird, Christopher P. Hebbes, Anushuya Tamang, Jonathon Mark Willets, Jonathan P. Thompson, Remo Guerrini, Girolamo Calo, David G. Lambert
Summary: In this study, the role of N/OFQ-NOP system was explored in freshly isolated volunteer human B- and T-cells incubated with LPS and PepG as a model of in vitro sepsis. The findings suggest that N/OFQ-NOP receptors play a regulatory role in B and T cell function, inhibiting cell migration and reducing GM-CSF release to variable degrees.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Multidisciplinary Sciences
Marianna Danielli, Roisin C. Thomas, Clare L. Gillies, David G. Lambert, Kamlesh Khunti, Bee Kang Tan
Summary: This study aimed to examine sVAP-1 as an early biomarker of pregnancy complications, especially hypertension during pregnancy. Data collected from blood sample analysis and hospital records showed that pregnant women with pregnancy-induced hypertension and gestational diabetes mellitus had reduced levels of sVAP-1, suggesting it may be a potential screening marker. Further research is needed to confirm its clinical applicability.