Whereas molecular mechanisms of cell desensitisation have been discussed at length in the literature, little organised information on the methods for studying desensitisation of cellular responses has been published. In this article, three commonly utilised protocols for studying homologous desensitisation of cellular responses are evaluated. These are (1) observation of attenuation of a response after an initial stimulus-induced activation, (2) repeated stimulation of cells after washing away the previous stimulus, and (3) repeated stimulation without a wash step. Advantages and limitations of each protocol are discussed and data is presented demonstrating some of the properties of the protocols.
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http://dx.doi.org/10.1006/phrs.1998.0294 | DOI Listing |
Mol Metab
January 2025
Section of Endocrinology and Investigative Medicine, Imperial College London, United Kingdom. Electronic address:
Objectives: There is renewed interest in targeting the glucose-dependent insulinotropic polypeptide receptor (GIPR) for treatment of obesity and type 2 diabetes. G-protein coupled receptor desensitisation is suggested to reduce the long-term efficacy of glucagon-like-peptide 1 receptor (GLP-1R) agonists and may similarly affect the efficacy of GIPR agonists. We explored the extent of pancreatic GIPR functional desensitisation with sustained agonist exposure.
View Article and Find Full Text PDFBiochem Pharmacol
January 2025
Department of Biomedical Sciences, Tilman J. Fertitta Family College of Medicine, University of Houton, Houston, TX, 77204, USA. Electronic address:
Cannabidiol (CBD), a phytocannabinoid, has emerged as a promising candidate for addressing a wide array of symptoms. It has the ability to bind to multiple proteins and receptors, including 5-HT1AR, transient receptor potential vanilloid 1 (TRPV1), and cannabinoid receptors. However, CBD's pharmacodynamic interaction with 5-HT1AR and its medicinal outcomes are still debated.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
December 2024
School of Medical Sciences, Faculty of Medicine and Health, Brain and Mind Centre, The University of Sydney, Sydney, NSW 2006, Australia.
Recent discoveries have revealed that genetic variants in γ-aminobutyric acid type A (GABA) receptor subunits can lead to both gain-of-function (GOF) and loss-of-function (LOF) receptors. GABA receptors, however, have a pseudosymmetrical pentameric assembly, and curiously diverse functional outcomes have been reported for certain homologous variants in paralogous genes (paralogous variants). To investigate this, we assembled a cohort of 11 individuals harboring paralogous M1 proline missense variants in , , and Seven mutations (α1, α1, β2, β3, β3, γ2, and γ2) in α1β2/3γ2 receptors were analyzed using electrophysiological examinations and molecular dynamics simulations.
View Article and Find Full Text PDFPlant Cell
October 2024
Plant Immunity Research Group, RIKEN Center for Sustainable Resource Science (CSRS), Yokohama, Kanagawa 230-0045, Japan.
Adv Sci (Weinh)
November 2024
Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China.
Radiotherapy is a curative arsenal for prostate cancer (PCa), but radioresistance seriously compromises its effectiveness. Dysregulated RNA splicing factors are extensively involved in tumor progression. Nonetheless, the role of splicing factors in radioresistance remains largely unexplored in PCa.
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