TY - JOUR AU - Turu, Gábor AU - Hunyady, László TI - Signal transduction of the CB1 cannabinoid receptor JF - JOURNAL OF MOLECULAR ENDOCRINOLOGY J2 - J MOL ENDOCRINOL VL - 44 PY - 2010 IS - 2 SP - 75 EP - 85 PG - 11 SN - 0952-5041 DO - 10.1677/JME-08-0190 UR - https://m2.mtmt.hu/api/publication/1252075 ID - 1252075 AB - The CB1 cannabinoid receptor (CB1R) is the major cannabinoid receptor in neuronal cells and the brain, but it also occurs in endocrine cells and other peripheral tissues. CB1R is a member of the superfamily of G protein- coupled receptors (GPCRs), which are characterized by seven transmembrane helices. The major mediators of CB1R are the G proteins of the Gi/o family, which inhibit adenylyl cyclases in most tissues and cells, and regulate ion channels, including calcium and potassium ion channels. Regulation of ion channels is an important component of neurotransmission modulation by endogenous cannabinoid compounds released in response to depolarization and Ca2+-mobilizing hormones. However, evidences exist that CB1Rs can also stimulate adenylyl cyclase via Gs, induce receptor-mediated Ca2+ fluxes and stimulate phospholipases in some experimental models. Stimulation of CB1R also leads to phosphorylation and activation of mitogen- activated protein kinases (MAPK), such as p42/p44 MAPK, p38 MAPK and c-Jun N- terminal kinase (JNK), which can regulate nuclear transcription factors. Activated and phosphorylated CB1Rs also associate with beta-arrestin molecules, which can induce the formation of signalling complexes and participate in the regulation of GPCR signalling. Recent data also suggest that CB1Rs can form homo- and heterodimers/oligomers, and the altered pharmacological properties of these receptor complexes may explain the pharmacological differences observed in various tissues. LA - English DB - MTMT ER - TY - JOUR AU - Turu, Gábor AU - Várnai, Péter AU - Gyombolai, Pál AU - Szidonya, László AU - Offertaler, L AU - Bagdy, György AU - Kunos, G AU - Hunyady, László TI - Paracrine transactivation of the CB1 cannabinoid receptor by AT1 angiotensin and other Gq/11 protein-coupled receptors. JF - JOURNAL OF BIOLOGICAL CHEMISTRY J2 - J BIOL CHEM VL - 284 PY - 2009 IS - 25 SP - 16914 EP - 16921 PG - 8 SN - 0021-9258 DO - 10.1074/jbc.M109.003681 UR - https://m2.mtmt.hu/api/publication/1235701 ID - 1235701 N1 - Department of Physiology, Faculty of Medicine, Semmelweis University, P. O. Box 259, H-1444 Budapest, Hungary Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892-9413, United States Department of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University, PO Box 259, H-1444 Budapest, Hungary Group of Neuropsychopharmacology, Semmelweis University, Hungarian Academy of Sciences, Budapest, Hungary Laboratory of Neurobiochemistry and Molecular Physiology, Hungary Cited By :60 Export Date: 15 December 2023 CODEN: JBCHA Correspondence Address: Hunyady, L.; Dept. of Physiology, P.O. Box 259, H-1444 Budapest, Hungary; email: Hunyady@eok.sote.hu AB - Intracellular signaling systems of G protein-coupled receptors are well established, but their role in paracrine regulation of adjacent cells is generally considered as a tissue-specific mechanism. We have shown previously that AT(1) receptor (AT(1)R) stimulation leads to diacylglycerol lipase-mediated transactivation of co-expressed CB(1)Rs in Chinese hamster ovary cells. In the present study we detected a paracrine effect of the endocannabinoid release from Chinese hamster ovary, COS7, and HEK293 cells during the stimulation of AT(1) angiotensin receptors by determining CB(1) cannabinoid receptor activity with bioluminescence resonance energy transfer-based sensors of G protein activation expressed in separate cells. The angiotensin II-induced, paracrine activation of CB(1) receptors was visualized by detecting translocation of green fluorescent protein-tagged beta-arrestin2. Mass spectrometry analyses have demonstrated angiotensin II-induced stimulation of 2-arachidonoylglycerol production, whereas no increase of anandamide levels was observed. Stimulation of G(q/11)-coupled M(1), M(3), M(5) muscarinic, V(1) vasopressin, alpha(1a) adrenergic, B(2) bradykinin receptors, but not G(i/o)-coupled M(2) and M(4) muscarinic receptors, also led to paracrine transactivation of CB(1) receptors. These data suggest that, in addition to their retrograde neurotransmitter role, endocannabinoids have much broader paracrine mediator functions during activation of G(q/11)-coupled receptors. LA - English DB - MTMT ER - TY - JOUR AU - Palkovits, Miklós AU - Harvey-White, J AU - Liu, J AU - Kovács, Zsolt AU - Bobest, M AU - Lovas, Gábor AU - Bagó, Attila György AU - Kunos, G TI - Regional distribution and effects of postmortal delay on endocannabinoid content of the human brain JF - NEUROSCIENCE J2 - NEUROSCIENCE VL - 152 PY - 2008 IS - 4 SP - 1032 EP - 1039 PG - 8 SN - 0306-4522 DO - 10.1016/j.neuroscience.2008.01.034 UR - https://m2.mtmt.hu/api/publication/1120873 ID - 1120873 N1 - Neuromorphological and Neuroendocrine Research Laboratory, the Semmelweis University, the Hungarian Academy of Sciences, 1094 Budapest, Hungary Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892-9413, United States Department of Zoology, University of West Hungary, 9700 Szombathely, Hungary Markusovszky Hospital, 9700 Szombathely, Hungary Department of Neurology, Semmelweis University, 1083 Budapest, Hungary National Institute of Neurosurgery, 1145 Budapest, Hungary Cited By :43 Export Date: 13 July 2023 CODEN: NRSCD Correspondence Address: Palkovits, M.; Neuromorphological and Neuroendocrine Research Laboratory, , 1094 Budapest, Hungary; email: palkovits@ana.sote.hu Chemicals/CAS: anandamide, 94421-68-8; 2-arachidonylglycerol, 53847-30-6; anandamide, 94421-68-8; Arachidonic Acids; Glycerides; Polyunsaturated Alkamides Funding details: National Institutes of Health, NIH Funding details: National Institute on Alcohol Abuse and Alcoholism, NIAAA, Z01AA000350 Funding details: European Commission, EC, LSHM-CT-2004-503036 Funding text 1: This research was supported by EU Grant FP6, BNEII No. LSHM-CT-2004-503036 to the Human Brain Tissue Bank, Budapest (to M.P.) and funds from the Intramural Program of the NIH (to G.K.). AB - Tissue levels of anandamide (AEA) and 2-arachidonoylglycerol (2-AG) have been determined in 16 regions and nuclei from human brains, using liquid chromatography/in-line mass spectrometry. Measurements in brain samples stored at −80 °C for 2 months to 13 years indicated that endocannabinoids were stable under such conditions. In contrast, the postmortal delay had a strong effect on brain endocannabinoid levels, as documented in brain samples microdissected and frozen 1–6 h postmortem, and in neurosurgical samples 0, 5, 30, 60, 180 and 360 min after their removal from the brain. The tissue levels of AEA increased continuously and in a region-dependent manner from 1 h after death, increasing about sevenfold by 6 h postmortem. In contrast, concentrations of 2-AG, which were 10–100 times higher in human brain regions than those of AEA, rapidly declined: within the first hour, 2-AG levels dropped to 25–35% of the initial (‘0 min’) value, thereafter they remained relatively stable. As analyzed in samples removed 1–1.5 h postmortem, AEA levels ranged from a high of 96.3 fmol/mg tissue in the nucleus accumbens to a low of 25.0 fmol/mg in the cerebellum. 2-AG levels varied eightfold, from 8.6 pmol/mg in the lateral hypothalamus to 1.1 pmol/mg in the nucleus accumbens. Relative levels of AEA and 2-AG varied from region to region, with the 2-AG:AEA ratio being high in the sensory spinal trigeminal nucleus (140:1), the spinal dorsal horn (136:1) and the lateral hypothalamus (98:1) and low in the nucleus accumbens (16:1) and the striatum (31:1). The results highlight the pitfall of analyzing endocannabinoid content in brain samples of variable postmortal delay, and document differential distribution of the two main endocannabinoids in the human brain. LA - English DB - MTMT ER - TY - JOUR AU - Wittmann, Gábor AU - Deli, Levente AU - Kalló, Imre AU - Hrabovszky, Erik AU - Watanabe, M AU - Liposits, Zsolt AU - Fekete, Csaba TI - Distribution of type 1 cannabinoid receptor (CB1)-immunoreactive axons in the mouse hypothalamus JF - JOURNAL OF COMPARATIVE NEUROLOGY J2 - J COMP NEUROL VL - 503 PY - 2007 IS - 2 SP - 270 EP - 279 PG - 10 SN - 0021-9967 DO - 10.1002/cne.21383 UR - https://m2.mtmt.hu/api/publication/109710 ID - 109710 N1 - Department of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, 1083, Hungary Department of Anatomy, Hokkaido University School of Medicine, Sapporo, 060-8638, Japan Department of Neuroscience, Faculty of Information Technology, Pázmány Péter Catholic University, Budapest, 1083, Hungary Tupper Research Institute, Department of Medicine, New England Medical Center, Boston, MA 02111, United States Department of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, 43 Szigony St., Budapest, 1083, Hungary Cited By :98 Export Date: 13 March 2024 CODEN: JCNEA Correspondence Address: Fekete, C.; Department of Endocrine Neurobiology, 43 Szigony St., Budapest, 1083, Hungary; email: feketecs@koki.hu Chemicals/CAS: Endocannabinoids; Receptor, Cannabinoid, CB1 AB - Type 1 cannabinoid receptor (CB1) is the principal receptor for endocannabinoids in the brain; it mainly occurs in preterminal/terminal axons and mediates retrograde neuronal signaling mechanisms. A large body of physiological and electrophysiological evidence indicates the critical role of CB1 in the regulation of hypothalamic functions. Conversely, the distribution of CB1-containing axons in the hypothalamus is essentially unknown. Therefore, we have analyzed the distribution and the ultrastructural characteristics of the CB1-immunoreactive (IR) axons in the mouse hypothalamus by using an antiserum against the C-terminal 31 amino acids of the mouse CB1. We found that CB1-IR axons innervated densely the majority of hypothalamic nuclei, except for the suprachiasmatic and lateral mammillary nuclei, in which only scattered CB1-IR fibers occurred. CB1-IR innervation of the arcuate, ventromedial, dorsomedial, and paraventricular nuclei and the external zone of the median eminence corroborated the important role of CB1 in the regulation of energy homeostasis and neuroendocrine functions. Ultrastructural studies to characterize the phenotype of CB1-IR fibers established that most CB1 immunoreactivity appeared in the preterminal and terminal portions of axons. The CB1-IR boutons formed axospinous, axodendritic, and axosomatic synapses. Analysis of labeled synapses in the paraventricular and arcuate nuclei detected approximately equal numbers of symmetric and asymmetric specializations. In conclusion, the study revealed the dense and differential CB1-IR innervation of most hypothalamic nuclei and the median eminence of the mouse brain. At the ultrastructural level, CB1-IR axons established communication with hypothalamic neurons via symmetric and asymmetric synapses indicating the occurrence of retrograde signaling by endocannabinoids in hypothalamic neuronal networks. J. Comp. Neurol. 503:270-279, 2007. (c) 2007 Wiley-Liss, Inc. LA - English DB - MTMT ER - TY - JOUR AU - Freund, Tamás AU - Katona, István AU - Piomelli, D TI - Role of endogenous cannabinoids in synaptic signaling JF - PHYSIOLOGICAL REVIEWS J2 - PHYSIOL REV VL - 83 PY - 2003 SP - 1017 EP - 1066 PG - 50 SN - 0031-9333 DO - 10.1152/physrev.00004.2003 UR - https://m2.mtmt.hu/api/publication/109323 ID - 109323 N1 - Megjegyzés-25002785 Megjegyzés-21894621 Z9: 598 Cited By :1097 Export Date: 11 August 2019 CODEN: PHREA Correspondence Address: Freund, T.F.; Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony u.43, Budapest 8 H-1083, Hungary; email: freund@koki.hu Chemicals/CAS: cannabis, 8001-45-4, 8063-14-7; dronabinol, 7663-50-5 Cited By :1097 Export Date: 21 August 2019 CODEN: PHREA Correspondence Address: Freund, T.F.; Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony u.43, Budapest 8 H-1083, Hungary; email: freund@koki.hu Chemicals/CAS: cannabis, 8001-45-4, 8063-14-7; dronabinol, 7663-50-5 Cited By :1106 Export Date: 14 November 2019 CODEN: PHREA Correspondence Address: Freund, T.F.; Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony u.43, Budapest 8 H-1083, Hungary; email: freund@koki.hu Chemicals/CAS: cannabis, 8001-45-4, 8063-14-7; dronabinol, 7663-50-5 Cited By :1127 Export Date: 6 March 2020 CODEN: PHREA Correspondence Address: Freund, T.F.; Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony u.43, Budapest 8 H-1083, Hungary; email: freund@koki.hu Chemicals/CAS: cannabis, 8001-45-4, 8063-14-7; dronabinol, 7663-50-5 Cited By :1127 Export Date: 12 March 2020 CODEN: PHREA Correspondence Address: Freund, T.F.; Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony u.43, Budapest 8 H-1083, Hungary; email: freund@koki.hu Chemicals/CAS: cannabis, 8001-45-4, 8063-14-7; dronabinol, 7663-50-5 Cited By :1131 Export Date: 18 April 2020 CODEN: PHREA Correspondence Address: Freund, T.F.; Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony u.43, Budapest 8 H-1083, Hungary; email: freund@koki.hu Chemicals/CAS: cannabis, 8001-45-4, 8063-14-7; dronabinol, 7663-50-5 Cited By :1131 Export Date: 19 April 2020 CODEN: PHREA Correspondence Address: Freund, T.F.; Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony u.43, Budapest 8 H-1083, Hungary; email: freund@koki.hu Chemicals/CAS: cannabis, 8001-45-4, 8063-14-7; dronabinol, 7663-50-5 Cited By :1135 Export Date: 20 May 2020 CODEN: PHREA Correspondence Address: Freund, T.F.; Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony u.43, Budapest 8 H-1083, Hungary; email: freund@koki.hu Chemicals/CAS: cannabis, 8001-45-4, 8063-14-7; dronabinol, 7663-50-5 Cited By :1136 Export Date: 24 May 2020 CODEN: PHREA Correspondence Address: Freund, T.F.; Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony u.43, Budapest 8 H-1083, Hungary; email: freund@koki.hu Chemicals/CAS: cannabis, 8001-45-4, 8063-14-7; dronabinol, 7663-50-5 Cited By :1136 Export Date: 25 May 2020 CODEN: PHREA Correspondence Address: Freund, T.F.; Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony u.43, Budapest 8 H-1083, Hungary; email: freund@koki.hu Chemicals/CAS: cannabis, 8001-45-4, 8063-14-7; dronabinol, 7663-50-5 Cited By :1136 Export Date: 28 May 2020 CODEN: PHREA Correspondence Address: Freund, T.F.; Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony u.43, Budapest 8 H-1083, Hungary; email: freund@koki.hu Chemicals/CAS: cannabis, 8001-45-4, 8063-14-7; dronabinol, 7663-50-5 Cited By :1165 Export Date: 30 December 2020 CODEN: PHREA Correspondence Address: Freund, T.F.; Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony u.43, Budapest 8 H-1083, Hungary; email: freund@koki.hu Chemicals/CAS: cannabis, 8001-45-4, 8063-14-7; dronabinol, 7663-50-5 Funding details: National Institute of Neurological Disorders and Stroke, NINDS, R01NS030549, R37NS030549 Cited By :1175 Export Date: 9 March 2021 CODEN: PHREA Correspondence Address: Freund, T.F.; Institute of Experimental Medicine, Szigony u.43, Budapest 8 H-1083, Hungary; email: freund@koki.hu Chemicals/CAS: cannabis, 8001-45-4, 8063-14-7; dronabinol, 7663-50-5 Funding details: National Institute of Neurological Disorders and Stroke, NINDS, R01NS030549 Cited By :1177 Export Date: 23 March 2021 CODEN: PHREA Correspondence Address: Freund, T.F.; Institute of Experimental Medicine, Szigony u.43, Budapest 8 H-1083, Hungary; email: freund@koki.hu Chemicals/CAS: cannabis, 8001-45-4, 8063-14-7; dronabinol, 7663-50-5 Funding details: National Institute of Neurological Disorders and Stroke, NINDS, R01NS030549 Cited By :1178 Export Date: 1 April 2021 CODEN: PHREA Correspondence Address: Freund, T.F.; Institute of Experimental Medicine, Szigony u.43, Budapest 8 H-1083, Hungary; email: freund@koki.hu Chemicals/CAS: cannabis, 8001-45-4, 8063-14-7; dronabinol, 7663-50-5 Funding details: National Institute of Neurological Disorders and Stroke, NINDS, R01NS030549 Cited By :1178 Export Date: 6 April 2021 CODEN: PHREA Correspondence Address: Freund, T.F.; Institute of Experimental Medicine, Szigony u.43, Budapest 8 H-1083, Hungary; email: freund@koki.hu Chemicals/CAS: cannabis, 8001-45-4, 8063-14-7; dronabinol, 7663-50-5 Funding details: National Institute of Neurological Disorders and Stroke, NINDS, R01NS030549 Cited By :1179 Export Date: 20 April 2021 CODEN: PHREA Correspondence Address: Freund, T.F.; Institute of Experimental Medicine, Szigony u.43, Budapest 8 H-1083, Hungary; email: freund@koki.hu Chemicals/CAS: cannabis, 8001-45-4, 8063-14-7; dronabinol, 7663-50-5 Funding details: National Institute of Neurological Disorders and Stroke, NINDS, R01NS030549 Cited By :1197 Export Date: 7 September 2021 CODEN: PHREA Correspondence Address: Freund, T.F.; Institute of Experimental Medicine, Szigony u.43, Budapest 8 H-1083, Hungary; email: freund@koki.hu Chemicals/CAS: cannabis, 8001-45-4, 8063-14-7; dronabinol, 7663-50-5 Funding details: National Institute of Neurological Disorders and Stroke, NINDS, R01NS030549 LA - English DB - MTMT ER -