KEGG   PATHWAY: elk04723
Entry
elk04723                    Pathway                                
Name
Retrograde endocannabinoid signaling - Enhydra lutris kenyoni (northern sea otter)
Description
Endogenous cannabinoids (endocannabinoids) serve as retrograde messengers at synapses in various regions of the brain. The family of endocannabinoids includes at least five derivatives of arachidonic acid; the two best characterized are arachydonoyl ethanolamide (anandamide, AEA) and 2-arachydonoil glycerol (2AG). They are released from postsynaptic neurons upon postsynaptic depolarization and/or receptor activation. The released endocannabinoids then activate the CB1 receptors (CB1R) at presynaptic terminals and suppress the release of inhibitory transmitter GABA (depolarization-induced suppression of inhibition, DSI) or excitatory transmitter glutamate (depolarization-induced suppression of excitation, DSE) by inhibiting Ca2+ channels. Besides the well-known expression of the CB1R in the plasma membrane, this receptor is also present in mitochondrial membranes, where it reduces the mitochondrial respiration and contributes to DSI. Whereas DSI and DSE result in short-term synaptic plasticity, endocannabinoids also mediate long-term synaptic changes (eCB-LTD). Persistent activation of CB1 receptors over a period of minutes triggers eCB-LTD by a RIM1alpha-dependent mechanism.
Class
Organismal Systems; Nervous system
Pathway map
elk04723  Retrograde endocannabinoid signaling
elk04723

Other DBs
GO: 0071926
Organism
Enhydra lutris kenyoni (northern sea otter) [GN:elk]
Gene
111149966  vesicular glutamate transporter 2 [KO:K12302]
111160629  vesicular glutamate transporter 1 isoform X1 [KO:K12302]
111142222  vesicular glutamate transporter 3 isoform X1 [KO:K12302]
111140968  glutamate receptor 1 isoform X1 [KO:K05197]
111153762  glutamate receptor 2 isoform X1 [KO:K05198]
111157250  glutamate receptor 3 [KO:K05199]
111153760  glutamate receptor 4 isoform X1 [KO:K05200]
111159674  voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
111143738  voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
111150407  voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
111150995  voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
111147676  metabotropic glutamate receptor 1 isoform X1 [KO:K04603]
111154498  metabotropic glutamate receptor 5 [KO:K04604]
111153498  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
111141432  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
111162302  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
111141620  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
111150005  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
111144005  inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
111159979  inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
111152507  inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
111155331  N-acyl-phosphatidylethanolamine-hydrolyzing phospholipase D [KO:K13985] [EC:3.1.4.54]
111158087  protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
111162208  protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
111139613  protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
111149706  sn1-specific diacylglycerol lipase alpha [KO:K13806] [EC:3.1.1.116]
111145635  sn1-specific diacylglycerol lipase beta [KO:K13806] [EC:3.1.1.116]
111150791  prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
111144286  monoacylglycerol lipase ABHD6 [KO:K13700] [EC:3.1.1.23]
111143292  fatty-acid amide hydrolase 1 [KO:K15528] [EC:3.5.1.99]
111143537  fatty-acid amide hydrolase 1-like [KO:K15528] [EC:3.5.1.99]
111158829  cannabinoid receptor 1 isoform X1 [KO:K04277]
111155312  guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
111143783  guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
111143343  guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
111157367  guanine nucleotide-binding protein G(o) subunit alpha [KO:K04534]
111154601  guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 [KO:K04536]
111145586  guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 isoform X1 [KO:K04537]
111159773  guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 [KO:K07825]
111148588  guanine nucleotide-binding protein subunit beta-4 [KO:K04538]
111140421  guanine nucleotide-binding protein subunit beta-5 [KO:K04539]
111159618  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 isoform X1 [KO:K07826]
111149566  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3 [KO:K04540]
111160502  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4 [KO:K04541]
111143000  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 [KO:K04542]
111161718  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 [KO:K04543]
111160835  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8 [KO:K04544]
111145828  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10 [KO:K04545]
111147333  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 [KO:K04546]
111162432  uncharacterized LOC105372280 homolog [KO:K04347]
111142967  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12 [KO:K04347]
111156207  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13 [KO:K04547]
111147281  guanine nucleotide-binding protein G(T) subunit gamma-T1 [KO:K04548]
111151818  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2 [KO:K04549]
111143157  G protein-activated inward rectifier potassium channel 1 [KO:K04997]
111155756  G protein-activated inward rectifier potassium channel 2 [KO:K05000]
111139030  G protein-activated inward rectifier potassium channel 3 [KO:K05002]
111153936  G protein-activated inward rectifier potassium channel 4 [KO:K04999]
111162543  voltage-dependent P/Q-type calcium channel subunit alpha-1A isoform X1 [KO:K04344]
111145672  voltage-dependent N-type calcium channel subunit alpha-1B isoform X1 [KO:K04849]
111162236  LOW QUALITY PROTEIN: mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
111142759  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
111144860  mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
111158897  mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
111154016  mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
111152267  mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
111157625  mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
111157628  mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
111152183  mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
111157054  adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
111153427  adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
111154044  adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
111162403  adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
111155044  adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
111157825  adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
111157326  adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
111146667  adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
111156133  adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
111162516  cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
111143399  cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
111159087  monoglyceride lipase isoform X1 [KO:K01054] [EC:3.1.1.23]
111149612  NADH dehydrogenase [ubiquinone] flavoprotein 1, mitochondrial isoform X1 [KO:K03942] [EC:7.1.1.2]
111142406  NADH dehydrogenase [ubiquinone] flavoprotein 2, mitochondrial isoform X1 [KO:K03943] [EC:7.1.1.2]
111155738  NADH dehydrogenase [ubiquinone] flavoprotein 3, mitochondrial isoform X1 [KO:K03944]
111157253  NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1 [KO:K03945]
111140937  NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 2 [KO:K03946]
111139570  NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 3 [KO:K03947]
111152555  LOW QUALITY PROTEIN: cytochrome c oxidase subunit NDUFA4-like [KO:K03948]
111147374  cytochrome c oxidase subunit NDUFA4 [KO:K03948]
111160211  NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 4-like 2 [KO:K03948]
111154239  NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 5-like isoform X1 [KO:K03949]
111151938  NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 5 isoform X1 [KO:K03949]
111155596  NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 5-like [KO:K03949]
111157547  NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 6 isoform X1 [KO:K03950]
111161756  NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 7 [KO:K03951]
111145557  NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 8 [KO:K03952]
111159811  NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 9, mitochondrial [KO:K03953]
111161328  NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 10, mitochondrial [KO:K03954]
111162309  acyl carrier protein, mitochondrial [KO:K03955]
111161769  NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 11 [KO:K03956]
111142148  NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 12 isoform X1 [KO:K11352]
111143867  NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 13 [KO:K11353]
111148723  NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 1 [KO:K03957]
111151936  NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 2, mitochondrial [KO:K03958]
111141342  NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 3 [KO:K03959]
111148802  NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 4 isoform X1 [KO:K03960]
111147306  NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 5, mitochondrial isoform X1 [KO:K03961]
111146284  NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 6 isoform X1 [KO:K03962]
111162542  NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 7 [KO:K03963]
111145242  NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 8, mitochondrial isoform X1 [KO:K03964]
111146716  NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 9 isoform X1 [KO:K03965]
111156034  NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 10 [KO:K03966]
111150594  NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 11, mitochondrial [KO:K11351]
111141377  NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial [KO:K03934] [EC:7.1.1.2]
111138869  NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial [KO:K03935] [EC:7.1.1.2]
111149396  NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, mitochondrial [KO:K03936] [EC:7.1.1.2]
111141116  NADH dehydrogenase [ubiquinone] iron-sulfur protein 4, mitochondrial [KO:K03937]
111142993  NADH dehydrogenase [ubiquinone] iron-sulfur protein 5 [KO:K03938]
111153450  NADH dehydrogenase [ubiquinone] iron-sulfur protein 6, mitochondrial [KO:K03939]
111161695  NADH dehydrogenase [ubiquinone] iron-sulfur protein 7, mitochondrial [KO:K03940] [EC:7.1.1.2]
111149681  NADH dehydrogenase [ubiquinone] iron-sulfur protein 8, mitochondrial [KO:K03941] [EC:7.1.1.2]
111149131  NADH dehydrogenase [ubiquinone] 1 subunit C1, mitochondrial [KO:K03967]
111154340  NADH dehydrogenase [ubiquinone] 1 subunit C2 isoform X1 [KO:K03968]
111141928  vesicular inhibitory amino acid transporter [KO:K15015]
111152143  regulating synaptic membrane exocytosis protein 1 isoform X1 [KO:K15291]
111161924  gamma-aminobutyric acid receptor subunit alpha-5 [KO:K05175]
111149113  gamma-aminobutyric acid receptor subunit alpha-2 [KO:K05175]
111149120  gamma-aminobutyric acid receptor subunit alpha-4 isoform X1 [KO:K05175]
111139171  gamma-aminobutyric acid receptor subunit alpha-3 [KO:K05175]
111141067  gamma-aminobutyric acid receptor subunit alpha-1 [KO:K05175]
111141113  gamma-aminobutyric acid receptor subunit alpha-6 [KO:K05175]
111149058  gamma-aminobutyric acid receptor subunit beta-1 isoform X1 [KO:K05181]
111141129  LOW QUALITY PROTEIN: gamma-aminobutyric acid receptor subunit beta-2 [KO:K05181]
111161915  gamma-aminobutyric acid receptor subunit beta-3 isoform X1 [KO:K05181]
111161925  gamma-aminobutyric acid receptor subunit gamma-3 [KO:K05186]
111141021  gamma-aminobutyric acid receptor subunit gamma-2 isoform X1 [KO:K05186]
111149188  gamma-aminobutyric acid receptor subunit gamma-1 [KO:K05186]
111154882  gamma-aminobutyric acid receptor subunit delta [KO:K05184]
111139198  gamma-aminobutyric acid receptor subunit epsilon [KO:K05185]
111139218  gamma-aminobutyric acid receptor subunit theta [KO:K05192]
111141225  gamma-aminobutyric acid receptor subunit pi isoform X1 [KO:K05189]
111158815  gamma-aminobutyric acid receptor subunit rho-2 [KO:K05190]
111158823  gamma-aminobutyric acid receptor subunit rho-1 isoform X1 [KO:K05190]
111151629  gamma-aminobutyric acid receptor subunit rho-3 [KO:K05190]
Compound
C00025  L-Glutamate
C00076  Calcium cation
C00116  Glycerol
C00157  Phosphatidylcholine
C00165  Diacylglycerol
C00189  Ethanolamine
C00219  Arachidonate
C00238  Potassium cation
C00334  4-Aminobutanoate
C00350  Phosphatidylethanolamine
C00427  Prostaglandin H2
C00575  3',5'-Cyclic AMP
C00689  alpha,alpha'-Trehalose 6-phosphate
C01245  D-myo-Inositol 1,4,5-trisphosphate
C01330  Sodium cation
C11695  Anandamide
C13856  2-Arachidonoylglycerol
C19912  N-Arachidonoyl-phosphatidylethanolamine
C19913  Phospho-anandamide
Reference
PMID:17419048
  Authors
Hashimotodani Y, Ohno-Shosaku T, Kano M
  Title
Ca(2+)-assisted receptor-driven endocannabinoid release: mechanisms that associate presynaptic and postsynaptic activities.
  Journal
Curr Opin Neurobiol 17:360-5 (2007)
DOI:10.1016/j.conb.2007.03.012
Reference
PMID:21531987
  Authors
Ohno-Shosaku T, Tanimura A, Hashimotodani Y, Kano M
  Title
Endocannabinoids and retrograde modulation of synaptic transmission.
  Journal
Neuroscientist 18:119-32 (2012)
DOI:10.1177/1073858410397377
Reference
PMID:18084639
  Authors
Basavarajappa BS
  Title
Neuropharmacology of the endocannabinoid signaling system-molecular mechanisms, biological actions and synaptic plasticity.
  Journal
Curr Neuropharmacol 5:81-97 (2007)
DOI:10.2174/157015907780866910
Reference
PMID:16968947
  Authors
Pacher P, Batkai S, Kunos G
  Title
The endocannabinoid system as an emerging target of pharmacotherapy.
  Journal
Pharmacol Rev 58:389-462 (2006)
DOI:10.1124/pr.58.3.2
Reference
PMID:15340387
  Authors
Di Marzo V, Bifulco M, De Petrocellis L
  Title
The endocannabinoid system and its therapeutic exploitation.
  Journal
Nat Rev Drug Discov 3:771-84 (2004)
DOI:10.1038/nrd1495
Reference
PMID:17404373
  Authors
Hashimotodani Y, Ohno-Shosaku T, Kano M
  Title
Endocannabinoids and synaptic function in the CNS.
  Journal
Neuroscientist 13:127-37 (2007)
DOI:10.1177/1073858406296716
Reference
PMID:19126760
  Authors
Kano M, Ohno-Shosaku T, Hashimotodani Y, Uchigashima M, Watanabe M
  Title
Endocannabinoid-mediated control of synaptic transmission.
  Journal
Physiol Rev 89:309-80 (2009)
DOI:10.1152/physrev.00019.2008
Reference
PMID:19640475
  Authors
Regehr WG, Carey MR, Best AR
  Title
Activity-dependent regulation of synapses by retrograde messengers.
  Journal
Neuron 63:154-70 (2009)
DOI:10.1016/j.neuron.2009.06.021
Reference
PMID:17636069
  Authors
Benarroch E
  Title
Endocannabinoids in basal ganglia circuits: implications for Parkinson disease.
  Journal
Neurology 69:306-9 (2007)
DOI:10.1212/01.wnl.0000267407.79757.75
Reference
PMID:16085309
  Authors
Ohno-Shosaku T, Hashimotodani Y, Maejima T, Kano M
  Title
Calcium signaling and synaptic modulation: regulation of endocannabinoid-mediated synaptic modulation by calcium.
  Journal
Cell Calcium 38:369-74 (2005)
DOI:10.1016/j.ceca.2005.06.014
Reference
PMID:18801434
  Authors
Harkany T, Mackie K, Doherty P
  Title
Wiring and firing neuronal networks: endocannabinoids take center stage.
  Journal
Curr Opin Neurobiol 18:338-45 (2008)
DOI:10.1016/j.conb.2008.08.007
Reference
PMID:18515270
  Authors
Hosking RD, Zajicek JP
  Title
Therapeutic potential of cannabis in pain medicine.
  Journal
Br J Anaesth 101:59-68 (2008)
DOI:10.1093/bja/aen119
Reference
PMID:21187849
  Authors
Di Marzo V
  Title
Endocannabinoid signaling in the brain: biosynthetic mechanisms in the limelight.
  Journal
Nat Neurosci 14:9-15 (2011)
DOI:10.1038/nn.2720
Reference
PMID:18948642
  Authors
McPartland JM
  Title
The endocannabinoid system: an osteopathic perspective.
  Journal
J Am Osteopath Assoc 108:586-600 (2008)
DOI:10.7556/jaoa.2008.108.10.586
Reference
PMID:17553427
  Authors
Chevaleyre V, Heifets BD, Kaeser PS, Sudhof TC, Castillo PE
  Title
Endocannabinoid-mediated long-term plasticity requires cAMP/PKA signaling and RIM1alpha.
  Journal
Neuron 54:801-12 (2007)
DOI:10.1016/j.neuron.2007.05.020
Reference
PMID:19553483
  Authors
Lafourcade CA
  Title
Presynaptic mechanisms of endocannabinoid-mediated long-term depression in the hippocampus.
  Journal
J Neurophysiol 102:2009-12 (2009)
DOI:10.1152/jn.00441.2009
Reference
PMID:21328621
  Authors
Ueda N, Tsuboi K, Uyama T, Ohnishi T
  Title
Biosynthesis and degradation of the endocannabinoid 2-arachidonoylglycerol.
  Journal
Biofactors 37:1-7 (2011)
DOI:10.1002/biof.131
Reference
PMID:14978245
  Authors
Guo J, Ikeda SR
  Title
Endocannabinoids modulate N-type calcium channels and G-protein-coupled inwardly rectifying potassium channels via CB1 cannabinoid receptors heterologously expressed in mammalian neurons.
  Journal
Mol Pharmacol 65:665-74 (2004)
DOI:10.1124/mol.65.3.665
Reference
PMID:22388959
  Authors
Benard G, Massa F, Puente N, Lourenco J, Bellocchio L, Soria-Gomez E, Matias I, Delamarre A, Metna-Laurent M, Cannich A, Hebert-Chatelain E, Mulle C, Ortega-Gutierrez S, Martin-Fontecha M, Klugmann M, Guggenhuber S, Lutz B, Gertsch J, Chaouloff F, Lopez-Rodriguez ML, Grandes P, Rossignol R, Marsicano G
  Title
Mitochondrial CB(1) receptors regulate neuronal energy metabolism.
  Journal
Nat Neurosci 15:558-64 (2012)
DOI:10.1038/nn.3053
Reference
PMID:26260530
  Authors
Busquets-Garcia A, Desprez T, Metna-Laurent M, Bellocchio L, Marsicano G, Soria-Gomez E
  Title
Dissecting the cannabinergic control of behavior: The where matters.
  Journal
Bioessays 37:1215-25 (2015)
DOI:10.1002/bies.201500046
Reference
PMID:28076767
  Authors
Harkany T, Horvath TL
  Title
(S)Pot on Mitochondria: Cannabinoids Disrupt Cellular Respiration to Limit Neuronal Activity.
  Journal
Cell Metab 25:8-10 (2017)
DOI:10.1016/j.cmet.2016.12.020
Reference
PMID:22449955
  Authors
Alger BE, Tang AH
  Title
Do cannabinoids reduce brain power?
  Journal
Nat Neurosci 15:499-501 (2012)
DOI:10.1038/nn.3072
Related
pathway
elk00190  Oxidative phosphorylation
elk04020  Calcium signaling pathway
elk04721  Synaptic vesicle cycle
elk04724  Glutamatergic synapse
elk04727  GABAergic synapse
KO pathway
ko04723   
LinkDB

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