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The eukaryotic elongation factor 2 kinase inhibitor, A484954, induces hypoglycaemic and hypotensive effects.
Br J Pharmacol
January 2025
Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Towada, Japan.
Background And Purpose: Eukaryotic elongation factor 2 kinase (eEF2K) belongs to the Ca/calmodulin-dependent protein kinase family. We previously revealed that A484954, a selective eEF2K inhibitor, caused hypotensive and diuretic effects via the production of nitric oxide (NO) in spontaneously hypertensive rats. Otsuka Long-Evans Tokushima Fatty (OLETF) rats are hypertensive because of obesity and type 2 diabetes.
View Article and Find Full Text PDFGPR88 impairs the signaling of kappa opioid receptors in a heterologous system and in primary striatal neurons.
Neuropharmacology
March 2025
Network Center for Biomedical Research in Neurodegenerative Diseases. CiberNed., Spanish National Health Institute Carlos iii, Av. Monforte de Lemos, 3-5, 28029, Madrid, Spain; Molecular Neurobiology Laboratory, Dept. Biochemistry and Molecular Biomedicine, Facultat de Biologia, Universitat de Barcelona, 08028, Barcelona, Spain; School of Chemistry, Universitat de Barcelona, Barcelona, Spain. Electronic address:
Article Synopsis
- GPR88 is an orphan G protein-coupled receptor primarily found in the striatum, and its function is not well understood despite changes in its expression seen in Parkinson's disease models.
- GPR88 was found to interact with the kappa-opioid receptor (KOR), and this interaction inhibits KOR-mediated signaling, as evidenced by experiments showing that GPR88 can modulate effects of KOR agonists in both cultured cells and primary striatal neurons.
- The GPR88-KOR complexes were more common in specific neurons related to dopamine pathways, suggesting that understanding their relationship could have implications for conditions like neuropathic pain, Parkinson's disease, and neuropsychiatric disorders.
Goreisan promotes diuresis by regulating the abundance of aquaporin 2 phosphorylated at serine 269 through calcium-sensing receptor activation.
Sci Rep
November 2024
TSUMURA Kampo Research Laboratories, Research & Development Division, TSUMURA & CO., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki, 300-1192, Japan.
Article Synopsis
- Aquaporin 2 (AQP2) is essential for water reabsorption and urine concentration, and its localization in kidney cells is influenced by anti-diuretic hormones, making it a target for specific medications.
- This study looked at how Goreisan (GRS), a traditional Japanese herbal medicine, affects urine production and AQP2 levels in mice, particularly under conditions induced by desmopressin.
- Findings revealed that GRS enhances diuretic effects by temporarily raising calcium levels in cells and decreasing the accumulation of phosphorylated AQP2 at the kidney's luminal surface, thus helping to regulate urine volume.
Utility of a Systolic Blood Pressure Polygenic Risk Score With Chlorthalidone Response.
JAMA Cardiol
December 2024
Department of Epidemiology, University of Alabama at Birmingham.
Article Synopsis
- A study investigated how well a polygenic risk score (PRS) for systolic blood pressure (SBP) can predict patients' responses to antihypertensive treatment and the risk of treatment-resistant hypertension.
- The research focused on participants from the GenHAT study, specifically Black individuals who were assigned to treatment groups involving chlorthalidone or lisinopril.
- The main outcomes measured were changes in blood pressure after six months and the likelihood of being classified as treatment-resistant hypertension based on defined criteria.
Glyceroniosomes for enhanced intestinal absorption of hydrochlorothiazide and lisinopril in their fixed dose combination.
Sci Rep
October 2024
Faculty of Pharmacy, Tanta University, Tanta, Egypt.
The objective was to investigate the effect of co-administration of hydrochlorothiazide and lisinopril as fixed dose combination on their intestinal absorption. The scope was extended to enhance intestinal absorption of both drugs. In situ rabbit intestinal absorption through the duodenum and jejuno-ileum was used to monitor membrane permeability of both drugs when perfused alone or in combination.
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