Drug addiction is a chronic and relapsing disorder that leads to compulsive drug intake despite deleterious consequences. By increasing dopamine (DA) in the mesolimbic system, drugs of abuse hijack the brain reward circuitry, which is critical for the development of enduring behavioral alterations. DA mainly acts onto DA D1 (D1R) and D2 (D2R) receptor subtypes, which are positively and negatively coupled to adenylyl cyclase, respectively. Extensive research has aimed at targeting these receptors for the treatment of addiction, however this often results in unwanted side-effects due to the implication of DA receptors in numerous physiological functions. A growing body of evidence indicates that the physical interaction of DA receptors with other receptors can finely tune their function, making DA receptor heteromers promising targets for more specific treatment strategies. An increasing number of articles highlighted the ability of both D1R and D2R to form heteromers, however, most studies carried out to date stem from observations in heterologous systems and the biological significance of DA receptor heteromers in vivo is only emerging. We focused this review on studies that were able to provide insights into functions on D1R and D2R heteromers in drug-evoked adaptations and discuss the limitations of current approaches to study receptor heteromers in vivo. This article is part of the Special Issue entitled 'Receptor heteromers and their allosteric receptor-receptor interactions'.
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http://dx.doi.org/10.1016/j.neuropharm.2018.12.003 | DOI Listing |
Int Immunopharmacol
December 2024
Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados del IPN, Unidad Sede Sur, Calzada de los Tenorios No. 235, Col. Granjas Coapa, Tlalpan, CP 14330 Mexico City, Mexico; Centro de Investigación sobre el Envejecimiento, Centro de Investigación y de Estudios Avanzados del IPN, Unidad Sede Sur, Calzada de los Tenorios No. 235, Col. Granjas Coapa, Tlalpan, CP 14330 Mexico City, Mexico. Electronic address:
Mast cells (MC) are crucial effectors in immediate allergic reactions. Monomeric IgE sensitizes MC and triggers various signaling responses. FcεRI/IgE/antigen crosslinking induces the release of several mediators, including bioactive lipids, but little is known about endocannabinoids (eCBs) secretion.
View Article and Find Full Text PDFJ Med Chem
January 2025
Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, Institute of Biomedicine of the University of Barcelona (IBUB), University of Barcelona, Barcelona 08028, Spain.
Activation of cannabinoid CB receptors (CBR) by agonists induces analgesia but also induces cognitive impairment through the heteromer formed between CBR and the serotonin 5HT receptor (5HTR). This side effect poses a serious drawback in the therapeutic use of cannabis for pain alleviation. Peptides designed from the transmembrane helices of CBR, which are predicted to bind 5HTR and alter the stability of the CBR-5HTR heteromer, have been shown to avert CBR agonist-induced cognitive impairment while preserving analgesia.
View Article and Find Full Text PDFCells
December 2024
Department of Anatomy, Cell Biology & Physiology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Background: TRPC5 proteins form plasma membrane cation channels and are expressed in the nervous and cardiovascular systems. TRPC5 activation leads to cell depolarization and increases neuronal excitability, whereas a homologous TRPC1 inhibits TRPC5 function via heteromerization. The mechanism underlying the inhibitory effect of TRPC1 in TRPC5/TRPC1 heteromers remains unknown.
View Article and Find Full Text PDFAndrology
December 2024
Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.
Background: Gonadotropins are glycoprotein hormones fundamental in the endocrine regulation of reproduction. They act on structurally similar members of G protein-coupled receptors (GPCRs) expressed exclusively in the gonads and support gametogenesis, sex steroid synthesis, and pregnancy. While it is a common opinion that the gonadotropin receptors act as a single molecule entity (monomer), increasing evidence underlines the formation of molecular complexes involving multiple receptors.
View Article and Find Full Text PDFNeuropharmacology
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:
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