43,218 results match your criteria selective antagonist


Chronic restraint stress induces changes in the cerebral Galpha 12/13 and Rho-GTPase signaling network.

Pharmacol Rep 2021 Jun 11. Epub 2021 Jun 11.

Department of Brain Biochemistry, Maj Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343, Kraków, Poland.

Background: Evidence indicates that Gα12, Gα13, and its downstream effectors, RhoA and Rac1, regulate neuronal morphology affected by stress. This study was aimed at investigating whether repeated stress influences the expression of proteins related to the Gα12/13 intracellular signaling pathway in selected brain regions sensitive to the effects of stress. Furthermore, the therapeutic impact of β(1)adrenergic receptors (β1AR) blockade was assessed. Read More

View Article and Full-Text PDF

P2X3 receptors participate in purinergic inhibition of gastrointestinal smooth muscle.

Authors:
Brian F King

Auton Neurosci 2021 Jun 5;234:102830. Epub 2021 Jun 5.

University College London (UCL), Research Department of Neuroscience, Pharmacology & Physiology (NPP), Gower Street, London WC1E 6BT, United Kingdom. Electronic address:

The ATP analogue α,β-meATP is a potent relaxant of gastrointestinal smooth muscle, but its molecular target is uncertain inside the gut. α,β-meATP relaxed the carbachol-precontracted guinea-pig taenia coli in a concentration-dependent manner (EC, 2.0 ± 0. Read More

View Article and Full-Text PDF

Stereotypy and spontaneous alternation in deer mice and its response to anti-adenosinergic intervention.

J Neurosci Res 2021 Jun 11. Epub 2021 Jun 11.

Center of Excellence for Pharmaceutical Sciences, Department of Pharmacology, Faculty of Health Sciences, North-West University, Potchefstroom, South Africa.

Repetitive behavioral phenotypes are a trait of several neuropsychiatric disorders, including obsessive-compulsive disorder (OCD). Such behaviors are typified by complex interactions between cognitive and neurobiological processes which most likely contribute to the suboptimal treatment responses often observed. To this end, exploration of the adenosinergic system may be useful, since adenosine-receptor modulation has previously shown promise to restore control over voluntary behavior and improve cognition in patients presenting with motor repetition. Read More

View Article and Full-Text PDF

The α2AR/Caveolin-1/p38MAPK/NF-κB axis explains dexmedetomidine protection against lung injury following intestinal ischaemia-reperfusion.

J Cell Mol Med 2021 Jun 10. Epub 2021 Jun 10.

Department of Anesthesiology, The First Affiliated Hospital of Nanchang University, Nanchang, China.

Intestinal ischaemia-reperfusion (I/R) injury can result in acute lung injury due to ischaemia and hypoxia. Dexmedetomidine (Dex), a highly selective alpha2-noradrenergic receptor (α2AR) agonist used in anaesthesia, is reported to regulate inflammation in organs. This study aimed to investigate the role and mechanism of Dex in lung injury caused by intestinal I/R. Read More

View Article and Full-Text PDF

BCL-2 Inhibition as Treatment for Chronic Lymphocytic Leukemia.

Curr Treat Options Oncol 2021 Jun 10;22(8):66. Epub 2021 Jun 10.

Bone Marrow Transplantation Unit, Hospital Israelita Albert Einstein, Av. Albert Einstein (SP), São Paulo, 627/520, Brazil.

Opinion Statement: At the end of the 1990s, with the advent of imatinib for chronic myeloid leukemia and rituximab for B cell lymphoproliferative diseases with CD20 expression, there was a great conceptual evolution in the treatment of onco-hematological diseases. Researchers from around the world and the pharmaceutical industry began to focus their efforts on the so-called target therapy used alone or associated with classic chemotherapeutic drugs. In chronic lymphocytic leukemia, the development of second-generation anti-CD20 antibodies, biosimilars, PI3K (phosphatidylinositol 3-kinases) inhibitors, BTK (Bruton's tyrosine kinase) inhibitors, and anti-bcl 2 drugs represented mainly by venetoclax brought new, broader, and more effective opportunities in the treatment of this disease. Read More

View Article and Full-Text PDF

Programmed Cell Death 10 Mediated CXCL2-CXCR2 Signaling in Regulating Tumor-Associated Microglia/Macrophages Recruitment in Glioblastoma.

Front Immunol 2021 24;12:637053. Epub 2021 May 24.

Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Programmed cell death 10 (PDCD10) plays a crucial role in regulating tumor phenotyping, especially in glioblastoma (GBM). Glioma-associated microglia/macrophages (GAMs) in tumor pathological microenvironment contribute to GBM progression. We previously found that the infiltration of GAMs was associated with PDCD10 expression in GBM patients. Read More

View Article and Full-Text PDF

Dexmedetomidine Inhibits ASIC Activity Activation of α Adrenergic Receptors in Rat Dorsal Root Ganglion Neurons.

Front Pharmacol 2021 24;12:685460. Epub 2021 May 24.

Research Center of Basic Medical Sciences, School of Basic Medical Sciences, Hubei University of Science and Technology, Xianning, China.

Dexmedetomidine (DEX), a selective α adrenergic receptor (α-AR) agonist, has been shown to have peripheral analgesic effects in a variety of pain conditions. However, the precise molecular mechanisms have not yet been fully elucidated. Acid sensing ion channels (ASICs) are the major player in pain associated with tissue acidosis. Read More

View Article and Full-Text PDF

GPR120 signaling controls amyloid-β degrading activity of matrix metalloproteinases.

J Neurosci 2021 Jun 4. Epub 2021 Jun 4.

Laboratory of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan

Alzheimer disease (AD) is characterized by the extensive deposition of amyloid-β peptide (Aβ) in the brain. Brain Aβ level is regulated by a balance between Aβ production and clearance. The clearance rate of Aβ is decreased in the brains of sporadic AD patients, indicating that the dysregulation of Aβ clearance mechanisms affects the pathological process of AD. Read More

View Article and Full-Text PDF

Pharmacokinetic and pharmacodynamic interactions between daridorexant, a dual orexin receptor antagonist, and citalopram in healthy subjects.

Eur Neuropsychopharmacol 2021 Jun 4;51:90-104. Epub 2021 Jun 4.

Department of Clinical Pharmacology, Idorsia Pharmaceuticals Ltd, Allschwil, Switzerland.

Daridorexant (ACT-541468) is a new dual orexin receptor antagonist being evaluated for the treatment of insomnia, which is a common comorbidity of depression and anxiety. Therefore, daridorexant is likely to be administered concomitantly with agents (e.g. Read More

View Article and Full-Text PDF

XENOBIOTIC CONSTITUTIVE ANDROSTANE RECEPTOR (CAR) IS HIGHLY INDUCED IN PSORIASIS AND PROMOTES KERATINOCYTE PROLIFERATION.

J Invest Dermatol 2021 Jun 4. Epub 2021 Jun 4.

The Advanced Institute for Medical Sciences, Dalian Medical University, Dalian, China.

Psoriasis is a chronic inflammatory skin disease with abnormal epidermal proliferation. Xenobiotics contribute to the pathogenesis of psoriasis. The mechanism linking xenobiotic stimuli with epidermal proliferation remains largely unknown. Read More

View Article and Full-Text PDF

M2-AChR Mediates Rapid Antidepressant Effects of Scopolamine Through Activating the mTORC1-BDNF Signaling Pathway in the Medial Prefrontal Cortex.

Front Psychiatry 2021 17;12:601985. Epub 2021 May 17.

The National Clinical Research Center for Mental Disorder and Beijing Key Laboratory of Mental Disorder, Beijing Anding Hospital, Capital Medical University, Beijing, China.

Scopolamine, a non-selective muscarinic acetylcholine receptor (M1~5-AChR) antagonist, has rapid and robust antidepressant effects in humans and other species. However, which of the five M-AChRs mediates these therapeutic effects has not been fully identified. Several studies implicate M2-AChR as a potential antidepressant target of scopolamine. Read More

View Article and Full-Text PDF

[Glioblastoma].

Authors:
Shota Tanaka

No Shinkei Geka 2021 May;49(3):623-631

Department of Neurosurgery, Tokyo University.

Glioblastoma, the most malignant and most common form of glioma, is known to portend very poor prognosis with the median overall survival of approximately 1.5 years. Its treatment requires a multidisciplinary approach, which consists of maximal safe resection followed by radiotherapy and chemotherapy with temozolomide. Read More

View Article and Full-Text PDF

The avian central roles of alpha and beta oestrogen receptors on food intake.

J Anim Physiol Anim Nutr (Berl) 2021 Jun 3. Epub 2021 Jun 3.

Department of Basic Sciences, Faculty of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran.

In rodents, oestrogen reduces food intake centrally via alpha oestrogen receptors (αER). As there was no report about the central roles of oestrogen receptors of alpha and beta, on food intake behaviour in birds, we aimed at this subject. In the first experiment beta oestradiol, a specific beta oestrogen receptor (βER; 0, 2. Read More

View Article and Full-Text PDF

Mutual assistance of nucleus accumbens cannabinoid receptor-1 and orexin receptor-2 in response to nicotine: a single-unit study.

Res Pharm Sci 2021 Apr 5;16(2):173-181. Epub 2021 Mar 5.

Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, I.R. Iran.

Background And Purpose: The nucleus accumbens (NAc) express both orexin-2 receptor (OX2R) and cannabinoid receptor type 1 (CB1R). Orexin and cannabinoid regulate the addictive properties of nicotine. In this study, the effect of the CB1R blockade on the electrical activity of NAc neurons in response to nicotine, and its probable interaction with the OX2R in this event, within this area, were examined the single-unit recording. Read More

View Article and Full-Text PDF

Allosteric Antagonist Modulation of TRPV2 by Piperlongumine Impairs Glioblastoma Progression.

ACS Cent Sci 2021 May 14;7(5):868-881. Epub 2021 Apr 14.

Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisboa, Portugal.

The use of computational tools to identify biological targets of natural products with anticancer properties and unknown modes of action is gaining momentum. We employed self-organizing maps to deconvolute the phenotypic effects of piperlongumine (PL) and establish a link to modulation of the human transient receptor potential vanilloid 2 (hTRPV2) channel. The structure of the PL-bound full-length rat TRPV2 channel was determined by cryo-EM. Read More

View Article and Full-Text PDF

The Heat Sensing Trpv1 Receptor Is Not a Viable Anticonvulsant Drug Target in the Mouse Model of Dravet Syndrome.

Front Pharmacol 2021 17;12:675128. Epub 2021 May 17.

Lambert Initiative for Cannabinoid Therapeutics, Brain and Mind Centre, Sydney, NSW, Australia.

Cannabidiol has been approved for the treatment of drug-resistant childhood epilepsies including Dravet syndrome (DS). Although the mechanism of anticonvulsant action of cannabidiol is unknown, emerging data suggests involvement of the transient receptor potential cation channel subfamily V member 1 (Trpv1). Pharmacological and genetic studies in conventional seizure models suggest Trpv1 is a novel anticonvulsant target. Read More

View Article and Full-Text PDF

BDNF rescues aging-associated internal anal sphincter dysfunction.

Am J Physiol Gastrointest Liver Physiol 2021 06 2. Epub 2021 Jun 2.

Medicine, Division of Gastroenterology & Hepatology, Thomas Jefferson University, Philadelphia, Pennsylvania, United States.

Aging can lead to rectoanal incontinence due to internal anal sphincter (IAS) dysfunction, which is characterized by a decrease in IAS tone and contractility and an increase in non-adrenergic non-cholinergic (NANC) relaxation. We aimed to determine whether brain-derived neurotropic factor (BDNF) rescues this aging-associated IAS dysfunction (AAID). To do so, we studied the effects of BDNF on the basal and GPCR-stimulated IAS smooth muscle tone and on NANC relaxation in in Fischer 344 rats representing different age groups (26-month-old [aging] vs. Read More

View Article and Full-Text PDF

5-HT Serotonergic, α-Adrenergic and Opioidergic Receptors Mediate the Analgesic Efficacy of Vortioxetine in Mice.

Molecules 2021 May 28;26(11). Epub 2021 May 28.

Department of Pharmacology, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey.

Vortioxetine is a multimodal antidepressant drug that affects several brain neurochemicals and has the potential to induce various pharmacological effects on the central nervous system. Therefore, we investigated the centrally mediated analgesic efficacy of this drug and the mechanisms underlying this effect. Analgesic activity of vortioxetine (5, 10 and 20 mg/kg, ) was examined by tail-clip, tail-immersion and hot-plate tests. Read More

View Article and Full-Text PDF

Adenosine Signaling in Mast Cells and Allergic Diseases.

Int J Mol Sci 2021 May 14;22(10). Epub 2021 May 14.

Clinical and Experimental Respiratory Immunoallergy (IRCE), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain.

Adenosine is a nucleoside involved in the pathogenesis of allergic diseases. Its effects are mediated through its binding to G protein-coupled receptors: A1, A2a, A2b and A3. The receptors differ in the type of G protein they recruit, in the effect on adenylyl cyclase (AC) activity and the downstream signaling pathway triggered. Read More

View Article and Full-Text PDF

Choline-Sigma-1R as an Additional Mechanism for Potentiation of Orexin by Cocaine.

Int J Mol Sci 2021 May 13;22(10). Epub 2021 May 13.

Center for Substance Abuse Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.

Orexin A, an endogenous peptide involved in several functions including reward, acts via activation of orexin receptors OX and OX, Gq-coupled GPCRs. We examined the effect of a selective OX agonist, OXA (17-33) on cytosolic calcium concentration, [Ca], in neurons of nucleus accumbens, an important area in the reward circuit. OXA (17-33) increased [Ca] in a dose-dependent manner; the effect was prevented by SB-334867, a selective OX receptors antagonist. Read More

View Article and Full-Text PDF

Molecular Changes Underlying Genistein Treatment of Wound Healing: A Review.

Curr Issues Mol Biol 2021 May 17;43(1):127-141. Epub 2021 May 17.

Department of Biomedical Research, East-Slovak Institute of Cardiovascular Diseases, Inc., 040 11 Košice, Slovakia.

Estrogen deprivation is one of the major factors responsible for many age-related processes including poor wound healing in postmenopausal women. However, the reported side-effects of estrogen replacement therapy (ERT) have precluded broad clinical administration. Therefore, selective estrogen receptor modulators (SERMs) have been developed to overcome the detrimental side effects of ERT on breast and/or uterine tissues. Read More

View Article and Full-Text PDF

Angiotensinergic Neurotransmissions in the Medial Amygdala Nucleus Modulate Behavioral Changes in the Forced Swimming Test Evoked by Acute Restraint Stress in Rats.

Cells 2021 May 17;10(5). Epub 2021 May 17.

School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, SP 14800-903, Brazil.

We investigated the role of angiotensin II type 1 (AT receptor) and type 2 (AT receptor) and MAS receptors present in the medial amygdaloid nucleus (MeA) in behavioral changes in the forced swimming test (FST) evoked by acute restraint stress in male rats. For this, rats received bilateral microinjection of either the selective AT receptor antagonist losartan, the selective AT receptor antagonist PD123319, the selective MAS receptor antagonist A-779, or vehicle 10 min before a 60 min restraint session. Then, behavior in the FST was evaluated immediately after the restraint (15 min session) and 24 h later (5 min session). Read More

View Article and Full-Text PDF

Chronic Low-Dose Alcohol Consumption Attenuates Post-Ischemic Inflammation via PPARγ in Mice.

Int J Mol Sci 2021 May 12;22(10). Epub 2021 May 12.

Department of Cellular Biology and Anatomy, LSUHSC-Shreveport, Shreveport, LA 71130, USA.

Ischemic stroke is one of the leading causes of death and permanent disability in adults. Recently, we found that light alcohol consumption (LAC) suppresses post-ischemic inflammatory response, which plays an important role in ischemic brain damage. Our goal was to determine the role of peroxisome proliferator-activated receptor-gamma (PPARγ) in the anti-inflammatory effect of LAC against transient focal cerebral ischemia. Read More

View Article and Full-Text PDF

Activation of Peripheral Opioid Kappa1 Receptor Prevents Cardiac Reperfusion Injury.

Physiol Res 2021 Jun 1. Epub 2021 Jun 1.

Laboratory of Experimental Cardiology, Cardiology Research Institute, Tomsk National Research Medical Center, the Russian Academy of Sciences, Tomsk, Russia.

The role of opioid kappa1 and kappa2 receptors in reperfusion cardiac injury was studied. Male Wistar rats were subjected to a 45-min coronary artery occlusion followed by a 120-min reperfusion. Opioid kappa receptor agonists were administered intravenously 5 min before the onset of reperfusion, while opioid receptor antagonists were given 10 min before reperfusion. Read More

View Article and Full-Text PDF

The targetable nanoparticle [email protected] represses tumor growth and angiogenesis by downregulating the S1PR1/P-STAT3/VEGFA axis in triple-negative breast cancer.

J Nanobiotechnology 2021 May 31;19(1):165. Epub 2021 May 31.

State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200032, China.

Background: Overexpressed vascular endothelial growth factor A (VEGFA) and phosphorylated signal transducer and activator of transcription 3 (P-STAT3) cause unrestricted tumor growth and angiogenesis of breast cancer (BRCA), especially triple-negative breast cancer (TNBC). Hence, novel treatment strategy is urgently needed.

Results: We found sphingosine 1 phosphate receptor 1 (S1PR1) can regulate P-STAT3/VEGFA. Read More

View Article and Full-Text PDF

Electroacupuncture Ameliorates Acute Pancreatitis: A Role for the Vagus Nerve-Mediated Cholinergic Anti-Inflammatory Pathway.

Front Mol Biosci 2021 13;8:647647. Epub 2021 May 13.

Department of Critical Care Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.

Organ failure resulting from excessive inflammation is the leading cause of death in the early phase of acute pancreatitis (AP). The autonomic nervous system was reported to be involved in AP, and the vagus nerve could exert anti-inflammatory effects through α7 nicotinic acetylcholine receptor (α7nAChR) signaling. Acupuncture has been widely used in traditional Asian medicine, and recent studies suggested the inflammation modulating effect of electroacupuncture (EA) might be mediated by the autonomic nervous system. Read More

View Article and Full-Text PDF

Discovery of 1,5-Dihydro-4-imidazol-4-one Derivatives as Potent, Selective Antagonists of CXC Chemokine Receptor 2.

ACS Med Chem Lett 2021 May 8;12(5):836-845. Epub 2021 Apr 8.

Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, P.R. China.

CXC chemokine receptors 1 (CXCR1) and 2 (CXCR2) have been demonstrated to have critical roles in cancer metastasis. Because they share high homology sequences, it is still unclear how to design selective CXCR1 or CXCR2 antagonists. Based on a pharmacophore model we built, compound bearing a 1,5-dihydro-4-imidazol-4-one scaffold was identified as a selective CXCR2 antagonist with a low CXCR1 antagonism preference. Read More

View Article and Full-Text PDF

Radiosynthesis and Biological Evaluation of [F]R91150, a Selective 5-HT Receptor Antagonist for PET-Imaging.

ACS Med Chem Lett 2021 May 1;12(5):738-744. Epub 2021 Apr 1.

Forschungszentrum Jülich GmbH, Institute of Neuroscience and Medicine, INM-5, Nuclear Chemistry (INM-5), 52425 Jülich, Germany.

Serotonergic 5-HT receptors in cortical and forebrain regions are an important substrate for the neuromodulatory actions of serotonin in the brain. They have been implicated in the etiology of many neuropsychiatric disorders and serve as a target for antipsychotic, antidepressant, and anxiolytic drugs. Positron emission tomography imaging using suitable radioligands can be applied for quantification of receptor densities and receptor occupancy for therapy evaluation. Read More

View Article and Full-Text PDF

Effects of the GluN2B-selective antagonist Ro 63-1908 on acquisition and expression of methamphetamine conditioned place preference in male and female rats.

Drug Alcohol Depend 2021 May 26;225:108785. Epub 2021 May 26.

Department of Psychological Science, Northern Kentucky University, 1 Nunn Drive, Highland Heights, KY, 41099, USA.

Background: Methamphetamine abuse has increased significantly in recent years. Currently, there are no FDA-approved pharmacotherapies for the treatment of methamphetamine use disorder. The goal of the current study was to determine if the N-methyl-d-aspartate (NMDA) GluN2B-selective antagonist Ro 63-1908 can block the conditioned rewarding effects of methamphetamine as assessed in conditioned place preference (CPP). Read More

View Article and Full-Text PDF

The role of the mineralocorticoid receptor and mineralocorticoid-receptor-directed therapies in heart failure.

Endocrinology 2021 May 29. Epub 2021 May 29.

Baker Heart and Diabetes Institute, Cardiovascular Endocrinology Laboratory, Prahran, Australia.

Mineralocorticoid receptor (MR) antagonists (MRA), also referred to as aldosterone blockers, are now well recognised for their clinical benefit in patients with heart failure with reduced ejection fraction (HFrEF). Recent studies have also shown MRA can improve outcomes in patients with 'HFpEF', where the ejection fraction is preserved but left ventriclar filling is reduced. While the MR is a steroid hormone receptor best known for anti-natriuretic actions on electrolyte homeostasis in the distal nephron, it is now estalished that the MR has many physiological and pathophysiological roles in the heart, vasculature and other non-epithelial tissue types. Read More

View Article and Full-Text PDF