{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T23:02:55Z","timestamp":1791932575044,"version":"4.3.4"},"reference-count":66,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T00:00:00Z","timestamp":1637020800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003086","name":"Basque Government","doi-asserted-by":"publisher","award":["IT1230-19"],"award-info":[{"award-number":["IT1230-19"]}],"id":[{"id":"10.13039\/501100003086","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003329","name":"Ministry of Economy, Industry and Competitiveness","doi-asserted-by":"publisher","award":["CTQ2017-85686-R"],"award-info":[{"award-number":["CTQ2017-85686-R"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Numerous studies have investigated the roles of the type 1 cannabinoid receptor (CB1) in glutamatergic and GABAergic neurons. Here, we used the cell-type-specific CB1 rescue model in mice to gain insight into the organizational principles of plasma membrane targeting and G\u03b1i\/o protein signalling of the CB1 receptor at excitatory and inhibitory terminals of the frontal cortex and hippocampus. By applying biochemical fractionation techniques and Western blot analyses to synaptosomal membranes, we explored the subsynaptic distribution (pre-, post-, and extra-synaptic) and CB1 receptor compartmentalization into lipid and non-lipid raft plasma membrane microdomains and the signalling properties. These data infer that the plasma membrane partitioning of the CB1 receptor and its functional coupling to G\u03b1i\/o proteins are not biased towards the cell type of CB1 receptor rescue. The extent of the canonical G\u03b1i\/o protein-dependent CB1 receptor signalling correlated with the abundance of CB1 receptor in the respective cell type (glutamatergic versus GABAergic neurons) both in frontal cortical and hippocampal synaptosomes. In summary, our results provide an updated view of the functional coupling of the CB1 receptor to G\u03b1i\/o proteins at excitatory and inhibitory terminals and substantiate the utility of the CB1 rescue model in studying endocannabinoid physiology at the subcellular level.<\/jats:p>","DOI":"10.3390\/molecules26226897","type":"journal-article","created":{"date-parts":[[2021,11,17]],"date-time":"2021-11-17T02:42:28Z","timestamp":1637116948000},"page":"6897","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Subsynaptic Distribution, Lipid Raft Targeting and G Protein-Dependent Signalling of the Type 1 Cannabinoid Receptor in Synaptosomes from the Mouse Hippocampus and Frontal Cortex"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0703-162X","authenticated-orcid":false,"given":"Miquel","family":"Saumell-Esnaola","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, University of the Basque Country UPV\/EHU, 01006 Vitoria-Gasteiz, Spain"},{"name":"Bioaraba, Neurofarmacolog\u00eda Celular y Molecular, 01009 Vitoria-Gasteiz, Spain"},{"name":"Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University Mainz, 55128 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Barrondo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, University of the Basque Country UPV\/EHU, 01006 Vitoria-Gasteiz, Spain"},{"name":"Bioaraba, Neurofarmacolog\u00eda Celular y Molecular, 01009 Vitoria-Gasteiz, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Salud Mental (CIBERSAM), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7098-0986","authenticated-orcid":false,"given":"Gontzal","family":"Garc\u00eda del Ca\u00f1o","sequence":"additional","affiliation":[{"name":"Bioaraba, Neurofarmacolog\u00eda Celular y Molecular, 01009 Vitoria-Gasteiz, Spain"},{"name":"Department of Neurosciences, Faculty of Pharmacy, University of the Basque Country UPV\/EHU, 01006 Vitoria-Gasteiz, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Aranzazu","family":"Goicolea","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry, Faculty of Pharmacy, University of the Basque Country UPV\/EHU, 01006 Vitoria-Gasteiz, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6727-2674","authenticated-orcid":false,"given":"Joan","family":"Sall\u00e9s","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, University of the Basque Country UPV\/EHU, 01006 Vitoria-Gasteiz, Spain"},{"name":"Bioaraba, Neurofarmacolog\u00eda Celular y Molecular, 01009 Vitoria-Gasteiz, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Salud Mental (CIBERSAM), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beat","family":"Lutz","sequence":"additional","affiliation":[{"name":"Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University Mainz, 55128 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1548-7718","authenticated-orcid":false,"given":"Krisztina","family":"Monory","sequence":"additional","affiliation":[{"name":"Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University Mainz, 55128 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/j.neuron.2006.07.006","article-title":"The Endocannabinoid System Controls Key Epileptogenic Circuits in the Hippocampus","volume":"51","author":"Monory","year":"2006","journal-title":"Neuron"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/npp.2017.206","article-title":"CB1 Receptor Signaling in the Brain: Extracting Specificity from Ubiquity","volume":"43","author":"Bains","year":"2018","journal-title":"Neuropsychopharmacology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1038\/nn.2494","article-title":"Bimodal control of stimulated food intake by the endocannabinoid system","volume":"13","author":"Bellocchio","year":"2010","journal-title":"Nat. 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