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This Article Accepted manuscript (PDF) All Versions of this Article: JME-08-0190v1 44/2/75    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Hunyady, L. Articles by Turu, G. Search for Related Content PubMed PubMed Citation Articles by Hunyady, L. Articles by Turu, G.

L Hunyady, Dept. of Physiology, Semmelweis University, Budapest, H-1444, Hungary
G Turu, Dept. of Physiology, Semmelweis University, Budapest, Hungary

Correspondence: Laszlo Hunyady, Email: hunyady{at}puskin.sote.hu

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 β-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.