@article{MTMT:1252075, title = {Signal transduction of the CB1 cannabinoid receptor}, url = {https://m2.mtmt.hu/api/publication/1252075}, author = {Turu, Gábor and Hunyady, László}, doi = {10.1677/JME-08-0190}, journal-iso = {J MOL ENDOCRINOL}, journal = {JOURNAL OF MOLECULAR ENDOCRINOLOGY}, volume = {44}, unique-id = {1252075}, issn = {0952-5041}, abstract = {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.}, year = {2010}, eissn = {1479-6813}, pages = {75-85}, orcid-numbers = {Turu, Gábor/0000-0002-4421-3812; Hunyady, László/0000-0002-8438-7251} } @article{MTMT:1235701, title = {Paracrine transactivation of the CB1 cannabinoid receptor by AT1 angiotensin and other Gq/11 protein-coupled receptors.}, url = {https://m2.mtmt.hu/api/publication/1235701}, author = {Turu, Gábor and Várnai, Péter and Gyombolai, Pál and Szidonya, László and Offertaler, L and Bagdy, György and Kunos, G and Hunyady, László}, doi = {10.1074/jbc.M109.003681}, journal-iso = {J BIOL CHEM}, journal = {JOURNAL OF BIOLOGICAL CHEMISTRY}, volume = {284}, unique-id = {1235701}, issn = {0021-9258}, abstract = {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.}, year = {2009}, eissn = {1083-351X}, pages = {16914-16921}, orcid-numbers = {Turu, Gábor/0000-0002-4421-3812; Várnai, Péter/0000-0002-7777-806X; Bagdy, György/0000-0001-8141-3410; Hunyady, László/0000-0002-8438-7251} } @article{MTMT:1120873, title = {Regional distribution and effects of postmortal delay on endocannabinoid content of the human brain}, url = {https://m2.mtmt.hu/api/publication/1120873}, author = {Palkovits, Miklós and Harvey-White, J and Liu, J and Kovács, Zsolt and Bobest, M and Lovas, Gábor and Bagó, Attila György and Kunos, G}, doi = {10.1016/j.neuroscience.2008.01.034}, journal-iso = {NEUROSCIENCE}, journal = {NEUROSCIENCE}, volume = {152}, unique-id = {1120873}, issn = {0306-4522}, abstract = {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.}, year = {2008}, eissn = {1873-7544}, pages = {1032-1039}, orcid-numbers = {Palkovits, Miklós/0000-0003-0578-0387; Kovács, Zsolt/0000-0001-8571-5686} } @article{MTMT:109710, title = {Distribution of type 1 cannabinoid receptor (CB1)-immunoreactive axons in the mouse hypothalamus}, url = {https://m2.mtmt.hu/api/publication/109710}, author = {Wittmann, Gábor and Deli, Levente and Kalló, Imre and Hrabovszky, Erik and Watanabe, M and Liposits, Zsolt and Fekete, Csaba}, doi = {10.1002/cne.21383}, journal-iso = {J COMP NEUROL}, journal = {JOURNAL OF COMPARATIVE NEUROLOGY}, volume = {503}, unique-id = {109710}, issn = {0021-9967}, abstract = {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.}, year = {2007}, eissn = {1096-9861}, pages = {270-279}, orcid-numbers = {Liposits, Zsolt/0000-0002-3508-2750} } @article{MTMT:109323, title = {Role of endogenous cannabinoids in synaptic signaling}, url = {https://m2.mtmt.hu/api/publication/109323}, author = {Freund, Tamás and Katona, István and Piomelli, D}, doi = {10.1152/physrev.00004.2003}, journal-iso = {PHYSIOL REV}, journal = {PHYSIOLOGICAL REVIEWS}, volume = {83}, unique-id = {109323}, issn = {0031-9333}, year = {2003}, eissn = {1522-1210}, pages = {1017-1066} }