There is evidence to suggest that receptors with seven transmembrane domains can exist in G protein-activating conformations. It is not known how many activated receptor forms exist for each receptor. Furthermore, if there are multiple forms, does the chemical structure of the agonist determine which form dominates, and therefore, which response pathway is activated? This latter scheme is referred to as agonist-receptor trafficking, and is discussed in this, the second of two articles by Terry Kenakin. One way to approach these questions is to study receptors that couple to more than one G protein and, in essence, to try to allow the G protein to indicate the receptor state.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/s0165-6147(00)89032-x | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Leveraging long-acting IL-15 agonists for intratumoral delivery and enhanced antimetastatic activity.
Front Immunol
November 2024
ProLynx Inc., San Francisco, CA, United States.
Article Synopsis
- IL-15 agonists are promising immunotherapy options as they boost the growth of immune cells like natural killer (NK) and CD8 T cells, but they have a short duration in the body requiring frequent doses.
- A new approach using hydrogel microspheres (MS) was developed to extend the half-life of IL-15, which successfully increased its duration to about one week.
- The study found that the MS conjugate of another IL-15 agonist, RLI, had a shorter half-life of 30 hours and was effective in stimulating immune cells, but caused significant injection-site toxicity; thus, it was focused on for intra-tumoral therapy where such effects could be potentially beneficial.
Positive allosteric modulation of a GPCR ternary complex.
Sci Adv
September 2024
Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.
The activation of a G protein-coupled receptor (GPCR) leads to the formation of a ternary complex between agonist, receptor, and G protein that is characterized by high-affinity binding. Allosteric modulators bind to a distinct binding site from the orthosteric agonist and can modulate both the affinity and the efficacy of orthosteric agonists. The influence allosteric modulators have on the high-affinity active state of the GPCR-G protein ternary complex is unknown due to limitations on attempting to characterize this interaction in recombinant whole cell or membrane-based assays.
View Article and Find Full Text PDFAre carfentanil and acrylfentanyl naloxone resistant?
Front Psychiatry
February 2024
Neuroscience Institute, Allegheny Health Network, Pittsburgh, PA, United States.
The rapid rise in deaths since 2012 due to opioid poisoning is correlated with the proliferation of potent synthetic opioid agonists such as fentanyl, acrylfentanyl, and carfentanil. The efficacy of frontline antidotes such as naloxone in reversing such poisoning events has been questioned, and the possibility of naloxone-resistant synthetic opioids has been raised. In this manuscript, we applied techniques to establish the median effective inhibitory concentrations for fentanyl, acrylfentanyl, and carfentanil and subsequently evaluate naloxone's ability to reverse agonist-receptor interactions.
View Article and Find Full Text PDFEfficacy and safety of Mazdutide on weight loss among diabetic and non-diabetic patients: a systematic review and meta-analysis of randomized controlled trials.
Front Endocrinol (Lausanne)
March 2024
Department of Metabolism and Endocrinology, Endocrine and Metabolic Disease Center, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China.
Background: Overweight and obesity are increasing global public health problems. Mazdutide is a new dual agonist drug that can potentially reduce weight and blood glucose levels simultaneously. However, the synthesis of evidence on the efficacy and safety of this drug is scarce.
View Article and Find Full Text PDFRelugolix for the treatment of uterine fibroids.
Expert Opin Pharmacother
October 2020
Department of Clinical and Experimental Medicine, Unit of Obstetrics and Gynaecology, "Magna Graecia" University, Catanzaro, Italy.
Introduction: Uterine fibroids (UF) are benign tumors common in premenopausal women, with strong impact on the health-care systems. For many years, surgery represented the only therapy for symptomatic fibroids. However, clinicians are observing a switch from surgery to noninvasive methods; in particular, medical treatment has been shown to be efficacious in obtaining a bleeding reduction and in ameliorating patient conditions.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!