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Journal of Pharmacology and Experimental Therapeutics

https://read.qxmd.com/read/38902033/-oxytocin-attenuates-sympathetic-innervation-with-inhibition-of-cardiac-mast-cell-degranulation-in-rats-post-myocardial-infarction
#1
JOURNAL ARTICLE
Jie Yin, Ye Wang, Weizhong Han, Weili Ge, Qingxia Yu, Yanyan Jing, Wenju Yan, Qian Liu, Liping Gong, Suhua Yan, Shuanglian Wang, Xiaolu Li, Yan Li, Hesheng Hu
Sympathetic hyperinnervation is the leading cause of fatal ventricular arrhythmia (VA) following myocardial infarction (MI). Cardiac mast cells cause arrhythmias directly through degranulation. However, the role and mechanism of mast cell degranulation in sympathetic remodeling remain unknown. We investigated the role of oxytocin (OT) in stabilizing cardiac mast cells and improving sympathetic innervation in rats. MI was induced by coronary artery ligation. Western blotting, immunofluorescence, and toluidine staining of mast cells were performed to determine the expression and location of target protein...
June 20, 2024: Journal of Pharmacology and Experimental Therapeutics
https://read.qxmd.com/read/38866563/aav9-mediated-intra-striatal-delivery-of-gnao1-reduces-hyperlocomotion-in-gnao1-heterozygous-r209h-mutant-mice
#2
JOURNAL ARTICLE
Alex J Roy, Jeffrey R Leipprandt, Joseph R Patterson, Anna C Stoll, Christopher J Kemp, Zaipo-Tcheisian D Oula, Tyler Mola, Ana R Batista, Caryl E Sortwell, Miguel Sena-Esteves, Richard R Neubig
Mutations in the GNAO1 gene, which encodes the abundant brain G-protein Gαo , result in neurologic disorders characterized by developmental delay, epilepsy, and movement abnormalities. There are over 50 mutant alleles associated with GNAO1 disorders; the R209H mutation results in dystonia, choreoathetosis, and developmental delay without seizures. Mice heterozygous for the human mutant allele ( Gnao1 +/R209H ) exhibit hyperactivity in open field tests but no seizures. We developed self-complimentary adeno-associated virus vectors (scAAV9) expressing two splice variants of human GNAO1 Gαo isoforms 1 (Go A, GNAO1...
June 12, 2024: Journal of Pharmacology and Experimental Therapeutics
https://read.qxmd.com/read/38858092/therapeutic-targeting-of-full-length-interleukin-33-protein-levels-with-cell-permeable-decoy-peptides-attenuates-fibrosis-in-the-bleomycin-model-in-vivo
#3
JOURNAL ARTICLE
Sergei P Atamas, Virginia K Lockatell, Nevins W Todd, John C Papadimitriou, Violeta Rus, Katerina N Lugkey, Stefanie N Vogel, Vladimir Y Toshchakov, Irina G Luzina
Interleukin (IL)-33 has been shown to centrally regulate, among other processes, inflammation and fibrosis. Both intracellular full-length (FLIL33) precursor and extracellular mature cytokine (MIL33) forms exert such regulation, albeit differentially. Drug development efforts to target the IL-33 pathway have focused mostly on MIL33 and its specific cell-surface receptor, ST2, with limited attempts to negotiate the pathophysiological contributions from FLIL33. Furthermore, even a successful strategy for targeting MIL33 effects would arguably benefit from a simultaneous attenuation of the levels of FLIL33, which remains the continuous source of MIL33 supply...
June 10, 2024: Journal of Pharmacology and Experimental Therapeutics
https://read.qxmd.com/read/38858091/-the-intoxication-equivalency-of-11-hydroxy-%C3%AE-9-tetrahydrocannabinol-11-oh-thc-relative-to-%C3%AE-9-tetrahydrocannabinol-thc
#4
JOURNAL ARTICLE
Ayat Zagzoog, Kenzie Halter, Alayna M Jones, Nicole Bannatyne, Joshua Cline, Alexis Wilcox, Anna-Maria Smolyakova, Robert B Laprairie
Δ9 -tetrahydrocannabinol (THC) is a psychoactive phytocannabinoid found in the Cannabis sativa plant. THC is primarily metabolized into 11-hydroxy-Δ9 -tetrahydrocannabinol (11-OH-THC) and 11-nor-9-carboxy-Δ9 -tetrahydrocannabinol (COOH-THC), that may themselves be psychoactive. There is very little research-based evidence concerning the pharmacokinetics and pharmacodynamics of 11-OH-THC as an individual compound. Male C57BL/6 mice were treated with THC or 11-OH-THC via i.p injection, tail vein i...
June 10, 2024: Journal of Pharmacology and Experimental Therapeutics
https://read.qxmd.com/read/38858090/long-term-treatment-with-the-streptococcal-exotoxin-streptolysin-o-inhibits-vascular-smooth-muscle-contraction-by-inducing-inos-expression-in-endothelial-cells
#5
JOURNAL ARTICLE
Mihiro Seki, Masashi Mukohda, Hirotaka Tajima, Nayu Morikita, Ryuya Imai, Kazuhide Itaya, Risuke Mizuno, Hiroshi Ozaki
Streptolysin O (SLO), a bacterial toxin produced by common hemolytic streptococci, including Streptococcus pyogenes and resident microbiota, may be associated with inflammation in the cardiovascular system. We previously reported that short-term treatment with SLO at relatively high concentrations (10-1000 ng/mL) diminished acetylcholine-induced, endothelial-dependent relaxation in a concentration-dependent manner. However, the vascular function effects of long-term exposure to SLO at lower concentrations are poorly understood...
June 10, 2024: Journal of Pharmacology and Experimental Therapeutics
https://read.qxmd.com/read/38858089/-preclinical-systemic-pharmacokinetics-dose-proportionality-and-cns-distribution-of-the-atm-inhibitor-wsd0628-a-novel-radiosensitizer-for-the-treatment-of-brain-tumors
#6
JOURNAL ARTICLE
Sneha Rathi, Ju-Hee Oh, Wenjuan Zhang, Ann C Mladek, Darwin A Garcia, Zhiyi Xue, Danielle M Burgenske, Wenqiu Zhang, Jiayan Le, Wei Zhong, Jann N Sarkaria, William F Elmquist
Radiation therapy, a standard treatment option for many cancer patients, induces DNA double strand breaks (DSBs), leading to cell death. Ataxia telangiectasia mutated (ATM) kinase is a key regulator of DSB repair, and ATM inhibitors are being explored as radiosensitizers for various tumors, including primary and metastatic brain tumors. Efficacy of radiosensitizers for brain tumors may be influenced by a lack of effective drug delivery across the blood-brain barrier (BBB). The objective of this study was to evaluate the systemic pharmacokinetics and mechanisms that influence the CNS distribution of WSD0628, a novel and potent ATM inhibitor, in the mouse...
June 10, 2024: Journal of Pharmacology and Experimental Therapeutics
https://read.qxmd.com/read/38849143/proteomic-analysis-of-signaling-pathways-modulated-by-fabp5-in-macrophages
#7
JOURNAL ARTICLE
Faniya Doswell, John D Haley, Martin Kaczocha
While acute inflammation serves essential functions in maintaining tissue homeostasis, chronic inflammation is causally linked to many diseases. Macrophages are a major cell-type that orchestrates inflammatory processes. During inflammation, macrophages undergo polarization and activation, thereby mobilizing pro-inflammatory and anti-inflammatory transcriptional programs that regulate ensuing macrophage functions. Fatty acid binding protein 5 (FABP5) is a lipid chaperone highly expressed in macrophages. FABP5 deletion is implicated in driving macrophages towards an anti-inflammatory phenotype, yet signaling pathways regulated by macrophage-FABP5 have not been systematically profiled...
June 7, 2024: Journal of Pharmacology and Experimental Therapeutics
https://read.qxmd.com/read/38849142/pan-ampk-activation-protects-tubules-in-rat-ischemic-acute-kidney-injury
#8
JOURNAL ARTICLE
Henriette Frikke-Schmidt, Kamal Albarazanji, Jenson Qi, David Frederick, Janos Steffen, Shanker Kalyana-Sundaram, Rong Meng, Zheng Huang Devine, Tao Chen, Qiu Li, Fuyong Du, George Ho, Jianying Liu, Roseann Riley, Romer A Gonzalez-Villalobos, Raul C Camacho, Andrea R Nawrocki, Meghan Pryor, Min Lee, Victoria Wong, Rosalie Matico, Elsie Diaz, Daniel Krosky, Mark Wall, Elise Gao, Akshay A Shah, James Leonard, Mark Erion, Alessandro Pocai, Mark R Player
Acute Kidney Injury (AKI) is characterized by an abrupt decline in kidney function and has been associated with excess risks of death, kidney disease progression, and cardiovascular events. The kidney has a high energetic demand with mitochondrial health being essential to renal function and damaged mitochondria has been reported across AKI subtypes. 5' adenosine monophosphate-activated protein kinase (AMPK) activation preserves cellular energetics through improvement of mitochondrial function and biogenesis when ATP levels are low such as under ischemia-induced AKI...
June 7, 2024: Journal of Pharmacology and Experimental Therapeutics
https://read.qxmd.com/read/38849141/-discovery-of-aurovertin-b-as-a-potent-metastasis-inhibitor-against-triple-negative-breast-cancer-elucidating-the-complex-role-of-the-atf3-dusp1-axis
#9
JOURNAL ARTICLE
Jian-Jun Shen, Xi Yang, Meng Yu, Qing-Cui Li, Ru-Yu Wang, Wen-Yan Yu, Jia-Li Zhang, Yi-Li Chen, Wen-Ting Zhu, Jia Li, Zha-Jun Zhan, Rui Wu
Triple-negative breast cancer (TNBC) is characterized by high mortality rates primarily due to its propensity for metastasis. Addressing this challenge necessitates the development of effective antimetastatic therapies. This study aimed to identify natural compounds with potential antimetastatic properties mainly based on the high-throughput phenotypic screening system. This system, utilizing luciferase reporter gene assays combined with scratch wound assays, evaluates compounds based on their influence on the epithelial-mesenchymal transition (EMT) marker E-cadherin...
June 7, 2024: Journal of Pharmacology and Experimental Therapeutics
https://read.qxmd.com/read/38849140/-chronic-activation-of-%C3%AE-adrenergic-receptors-leads-to-tissue-water-and-electrolyte-retention
#10
JOURNAL ARTICLE
Steeve Akumwami, Kento Kitada, Yoshihide Fujisawa, Netish Kumar Kundo, Md Moshiur Rahman, Asahiro Morishita, Hiroaki Kitamura, Asadur Rahman, Yuichi Ogino, Akira Nishiyama
Beta-adrenergic receptors (β-AR) are expressed on the membranes of various cell types and their activation affects body water balance by modulating renal sodium and water excretion, cardiovascular function and metabolic processes. However, β-AR-associated body fluid imbalance has not been well characterised. In the present study, we hypothesized that chronic β-AR stimulation increases electrolyte and water content at the tissue level. We evaluated the effects of isoproterenol, a non-selective β-AR agonist, on electrolyte and water balance at the tissue level...
June 7, 2024: Journal of Pharmacology and Experimental Therapeutics
https://read.qxmd.com/read/38844365/role-of-mitogen-activated-protein-kinase-kinase-kinase-kinase-4-signaling-in-liver-and-metabolic-diseases
#11
JOURNAL ARTICLE
Felix Ampadu, Vibhudutta Awasthi, Aditya D Joshi
MAP4K4 is a serine/threonine protein kinase belonging to the germinal center kinase (GCK) sub-group of sterile 20 protein (Ste20p) family of kinases. MAP4K4 has been involved in regulating multiple biological processes and a plethora of pathologies, including systemic inflammation, cardiovascular diseases, cancers, metabolic and hepatic diseases. Recently, multiple reports have indicated the upregulation of MAP4K4 expression and signaling in hyperglycemia and liver diseases. This review summarizes our current understanding of MAP4K4 structure, expression, as well as its regulation and signaling, specifically in metabolic and hepatic diseases...
June 6, 2024: Journal of Pharmacology and Experimental Therapeutics
https://read.qxmd.com/read/38844364/the-national-center-for-complementary-and-integrative-health-nccih-priorities-for-cannabis-and-cannabinoid-research
#12
JOURNAL ARTICLE
David Shurtleff, Angela Arensdorf, Patrick C Still, Steven W Gust, Sekai Chideya, David Craig Hopp, Inna Belfer
The National Center for Complementary and Integrative Health (NCCIH), a component of the National Institutes of Health (NIH), has a broad interest in the study of the biological activities of natural products with a strong research emphasis on products for which there is compelling preclinical evidence for potential biological activity that may lead to a health benefit or treatment interventions, and/or products that are widely used by the American public. Use of cannabis for medical purposes is legal in 38 states and the District of Columbia...
June 6, 2024: Journal of Pharmacology and Experimental Therapeutics
https://read.qxmd.com/read/38844363/-sex-differences-in-the-neural-and-behavioral-effects-of-acute-high-dose-edible-cannabis-consumption-in-rats
#13
JOURNAL ARTICLE
Richard Quansah Amissah, Hakan Kayir, Malik Asfandyaar Talhat, Ahmad Hassan, Yu Gu, Ron Johnson, Karolina Urban, Jibran Y Khokhar
The consumption of D9-tetrahydrocannabinol (THC)- or cannabis-containing edibles has increased in recent years; however, the behavioral and neural circuit effects of such consumption remain unknown, especially in the context of ingestion of higher doses resulting in cannabis intoxication. We examined the neural and behavioral effects of acute high-dose edible cannabis consumption (AHDECC). Sprague-Dawley rats (6 males, 7 females) were implanted with electrodes in the prefrontal cortex (PFC), dorsal hippocampus (dHipp), cingulate cortex (Cg), and nucleus accumbens (NAc)...
June 6, 2024: Journal of Pharmacology and Experimental Therapeutics
https://read.qxmd.com/read/38834356/-select-minor-cannabinoids-from-cannabis-sativa-are-cannabimimetic-and-antinociceptive-in-a-mouse-model-of-chronic-neuropathic-pain
#14
JOURNAL ARTICLE
Abigail M Schwarz, Dea Kobeci, Joey Mancuso, Valeria Moreno-Rodriguez, Caleb Seekins, Thai Bui, Alyssa Welborn, Jerry Carr, John M Streicher
Chronic pain conditions affect nearly 20% of the population in the United States. Current medical interventions, such as opioid drugs, are effective at relieving pain but are accompanied by many undesirable side effects. This is one reason increased numbers of chronic pain patients have been turning to Cannabis for pain management. Cannabis contains many bioactive chemical compounds; however, current research looking into lesser-studied minor cannabinoids in Cannabis lacks uniformity between experimental groups and/or excludes female mice from investigation...
June 4, 2024: Journal of Pharmacology and Experimental Therapeutics
https://read.qxmd.com/read/38834355/the-minor-phytocannabinoid-delta-8-tetrahydrocannabinol-attenuates-collagen-induced-arthritic-inflammation-and-pain-depressed-behaviors
#15
JOURNAL ARTICLE
S Olivia Vanegas, Arsalan Zaki, Caroline N Dealy, Steven G Kinsey
Patients with arthritis report using cannabis for pain management, and the major cannabinoid Δ9 -THC has anti-inflammatory properties, yet the effects of minor cannabinoids on arthritis are largely unknown. The goal of the present study was to determine the antiarthritic potential of the minor cannabinoid Δ8 -THC using the collagen-induced arthritis (CIA) mouse model. Adult male DBA/1J mice were immunized and boosted 21 days later with an emulsion of collagen and complete Freund's adjuvant. Beginning on the day of the booster, mice were administered twice-daily injections of Δ8 -THC (3 or 30 mg/kg), the steroid dexamethasone (2 mg/kg), or vehicle for two weeks...
June 4, 2024: Journal of Pharmacology and Experimental Therapeutics
https://read.qxmd.com/read/38834354/-rapamycin-and-starvation-mitigate-indomethacin-induced-intestinal-damage-through-preservation-of-lysosomal-vacuolar-atpase-integrity
#16
JOURNAL ARTICLE
Makoto Shirakawa, Shunichi Yokoe, Takatoshi Nakagawa, Kazumasa Moriwaki, Toshihisa Takeuchi, Michio Asahi
Nonsteroidal anti-inflammatory drugs (NSAIDs) possess anti-inflammatory, antipyretic, and analgesic properties and are among the most commonly used drugs. Although the cause of NSAID-induced gastric ulcers is well-understood, the mechanism behind small intestinal ulcers remains elusive. In this study, we examined the mechanism through which indomethacin (IM), a prominent NSAID, induces small intestinal ulcers, both in vitro and in vivo In IEC6 cells, a small intestinal epithelial cell line, IM treatment elevated levels of LC3-Ⅱ and p62...
June 4, 2024: Journal of Pharmacology and Experimental Therapeutics
https://read.qxmd.com/read/38816229/tauroursodeoxycholic-acid-reverses-dss-induced-colitis-in-mice-via-modulation-of-intestinal-barrier-dysfunction-and-microbiome-dysregulation
#17
JOURNAL ARTICLE
Longbiao Luo, Yi Zhao, Guangji Zhang, Sijing Dong, YinYue Xu, Hehe Shi, Menggai Zhang, Xue Liu, SiCen Wang, Hua Luo, Wanghui Jing
Background: Ulcerative colitis (UC) is an immune-mediated inflammatory disease that can lead to persistent damage and even cancer without any intervention. Conventional treatments can alleviate UC symptoms but are costly and even cause various side effects. Tauroursodeoxycholic acid (TUDCA), a secondary bile acid derivative, possesses anti-inflammatory and cytoprotective properties for various diseases, but its potential therapeutic benefits in UC have not been fully explored. Methods: Mice were subjected to colitis induction using 3% dextran sulfate sodium (DSS)...
May 30, 2024: Journal of Pharmacology and Experimental Therapeutics
https://read.qxmd.com/read/38816228/high-dose-agomelatine-combined-to-haloperidol-decanoate-improves-cognition-downregulating-mt2-against-upregulating-d5-maintaining-kr%C3%A3-ppel-like-factor-9-though-alters-cardiac-electrophysiology
#18
JOURNAL ARTICLE
Sherine Abdelmissih, Marwa Abdelgwad, Doaa Mohamed Elroby Ali, Mohamed Sharif Ismail Negm, Mohamed Ali Eshra, Amal Youssef
Haloperidol decanoate (HD) was implicated in cognitive impairment. Agomelatine (AGO) was claimed to improve cognition. We aimed at investigating the effects of HD + low- or high- dose AGO on cognition, verifying the melatonergic/dopaminergic-to-the cholinergic hypothesis of cognition and exploring relevant cardiovascular issues in adult male Wistar albino rats. HD + high- dose AGO prolonged the step through latency by +61.47% ( ρ < 0.0001), increased the time spent in bright light by +439.49% ( ρ < 0...
May 30, 2024: Journal of Pharmacology and Experimental Therapeutics
https://read.qxmd.com/read/38777606/platelet-spreading-and-clot-retraction-are-regulated-by-two-distinct-%C3%AE-iib-%C3%AE-3-outside-in-signaling-pathways
#19
JOURNAL ARTICLE
Arjit Nigam, Voddarahally N Manjuprasanna, Meghna U Naik, Ulhas P Naik
Bi-directional signaling through platelet integrin αIIb β3 is essential in hemostasis and thrombosis. In quiescent platelets αIIb β3 is in a low-affinity ligand binding state. However, upon platelet activation by agonists through inside-out signaling, a rapid switch in the conformation of the integrin results in a high affinity ligand binding state capable of binding soluble fibrinogen. Ligand binding to the αIIb β3 induces a signaling termed outside-in signaling that regulate platelet spreading and clot retraction...
May 22, 2024: Journal of Pharmacology and Experimental Therapeutics
https://read.qxmd.com/read/38777605/-the-potential-of-cannabichromene-cbc-as-a-therapeutic-agent
#20
JOURNAL ARTICLE
Diana E Sepulveda, Kent E Vrana, Joshua J Kellogg, Jordan E Bisanz, Dhimant Desai, Nicholas M Graziane, Wesley M Raup-Konsavage
There is a growing interest in the use of medicinal plants to treat a variety of diseases, and one of the most commonly used medicinal plants globally is Cannabis sativa The two most abundant cannabinoids (Δ9 -tetrahydrocannabinol and cannabidiol) have been governmentally approved to treat selected medical conditions; however, the plant produces over 100 cannabinoids, including cannabichromene (CBC). While the cannabinoids share a common precursor molecule, cannabigerol, they are structurally and pharmacologically unique...
May 22, 2024: Journal of Pharmacology and Experimental Therapeutics
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