title: Regulation of endocannabinoid release by G proteins: a paracrine mechanism of G protein-coupled receptor action.
abstract: In the past years, the relationship between the endocannabinoid system (ECS) and other hormonal and neuromodulatory systems has been intensively studied. G protein-coupled receptors (GPCRs) can stimulate endocannabinoid (eCB) production via activation of G(q/11) proteins and, in some cases, G(s) proteins. In this review, we summarize the pathways through which GPCR activation can trigger eCB release, as well as the best known examples of this process throughout the body tissues. Angiotensin II-induced activation of AT(1) receptors, similar to other G(q/11)-coupled receptors, can lead to the formation of 2-arachidonoylglycerol (2-AG), an important eCB. The importance of eCB formation in angiotensin II action is supported by the finding that the hypertensive effect of angiotensin II, injected directly into the hypothalamic paraventricular nucleus of anaesthetized rats, can be abolished by AM251, an inverse agonist of CB(1) cannabinoid receptors (CB(1)Rs). We conclude that activation of the ECS should be considered as a general consequence of the stimulation of G(q/11)-coupled receptors, and may mediate some of the physiological effects of GPCRs.
authors.affiliation: Department of Physiology, Semmelweis University, Budapest, Hungary.
authors.forename: Pál
authors.initials: P
authors.lastname: Gyombolai
authors.forename: Dorottya
authors.initials: D
authors.lastname: Pap
authors.forename: Gábor
authors.initials: G
authors.lastname: Turu
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Catt
authors.forename: György
authors.initials: G
authors.lastname: Bagdy
authors.forename: László
authors.initials: L
authors.lastname: Hunyady
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D063388:Endocannabinoids; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism*; D005989:Glycerides / Q000378:metabolism*; D006801:Humans; D019899:Paracrine Communication / Q000502:physiology*; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000378:metabolism*
chemical_list: D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D005989:Glycerides; D010880:Piperidines; D011720:Pyrazoles; D044140:Receptor, Angiotensin, Type 1; D043884:Receptor, Cannabinoid, CB1; D000804:Angiotensin II; C103505:AM 251; C094503:glyceryl 2-arachidonate; D043802:GTP-Binding Protein alpha Subunits, Gq-G11
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