Cellular signal transduction by anandamide and 2-arachidonoylglycerol.
Anandamide (arachidonylethanolamide) and 2-arachidonoylglycerol mediate many of their actions via either CB(1) or CB(2) cannabinoid receptor subtypes. These agonist-receptor interactions result in activation of G proteins, particularly those of the G(i/o) family. Signal transduction pathways that are regulated by these G proteins include inhibition of adenylyl cyclase, regulation of ion currents (inhibition of voltage-gated L, N and P/Q Ca(2+)-currents; activation of K(+) currents); activation of focal adhesion kinase (FAK), mitogen activated protein kinase (MAPK) and induction of immediate early genes; and stimulation of nitric oxide synthase (NOS). Other effects of anandamide and/or 2-arachidonoylglycerol that are not mediated via cannabinoid receptors include inhibition of L-type Ca(2+) channels, stimulation of VR(1) vanilloid receptors, transient changes in intracellular Ca(2+), and disruption of gap junction function. Cardiovascular regulation by anandamide appears to occur by a variety of receptor-mediated and non-receptor-mediated mechanisms. This review will describe and evaluate each of these signal transduction pathways and mechanisms.
Howlett
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Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, 1402 South Grand Blvd, St. Louis, MO 63104, USA. ahowlett@wpo.nccu.edu
Mukhopadhyay
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D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D063388:Endocannabinoids; D017629:Gap Junctions / Q000187:drug effects; D005989:Glycerides / Q000494:pharmacology*; D006801:Humans; D053284:Polyunsaturated Alkamides; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*
D001095:Arachidonic Acids; D063388:Endocannabinoids; D005989:Glycerides; D053284:Polyunsaturated Alkamides; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; C094503:glyceryl 2-arachidonate; D002118:Calcium; C078814:anandamide