Signal transduction interactions between CB1 cannabinoid and dopamine receptors in the rat and monkey striatum

Meschler, Justin P.; Howlett, Allyn C.

doi:10.1016/s0028-3908(01)00012-0

Cited by 96 publications

(72 citation statements)

References 31 publications

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“…For example, Meschler and Howlett (2001), working with synaptosomes isolated from rat and monkey brains, found that independent activation of either CB1 receptor or D2 inhibited cAMP accumulation; however, they did not find that coactivation of these receptors prevented the inhibition. Glass and Felder (1997) used primary cultures of striatal neurons and of Chinese hamster ovary cells expressing the CB1 receptor.…”

Section: Discussionmentioning

confidence: 99%

Cannabinoid Agonists Stimulate [³H]GABA Release in the Globus Pallidus of the Rat When G_iProtein-Receptor Coupling Is Restricted: Role of Dopamine D2 Receptors

González¹,

Paz²,

Florán³

et al. 2008

J Pharmacol Exp Ther

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The motor effects of cannabinoids in the globus pallidus appear to be caused by increases in interstitial GABA. To elucidate the mechanism of this response, we investigated the effect of the selective cannabinoid type 1 receptor (CB1) cannabinoid agonist arachidonyl-2-chloroethylamide (ACEA) on [ 3 H]GABA release in slices of the rat globus pallidus. ACEA had two effects: concentrations between 10 Ϫ8 and 10 Ϫ6 M stimulated release, whereas higher concentrations (IC 50 Ϸ 10 Ϫ6 M) inhibited it. Another cannabinoid agonist, WIN-55,212-2, also had bimodal effects on release. Studies of cAMP production indicate that under conditions of low G i/o , availability the coupling of CB1 receptors with G i/o proteins can be changed into CB1:G s/olf coupling; therefore, we determined the effects of conditions that limit G i/o availability on (S)-5-aminosulfonyl-N-[(1-ethyl-2-pyrrolidinyl)methyl]-2-methoxybenzamidersqb]or depleting dopamine with reserpine inhibited the ACEA-induced stimulation of release. Thus, the D2 dependence of stimulation is consistent with the proposal that D2 receptors reduce G i/o proteins available for binding to the CB1 receptor. In summary, CB1 receptor activation has dual effects on GABA release in the globus pallidus. Low concentrations stimulate release through a process that depends on activation of dopamine D2 receptors that may limit G i/o protein availability. Higher concentrations of cannabinoid inhibit GABA release through mechanisms that are independent of D2 receptor activation.

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Section: Discussionmentioning

confidence: 99%

Cannabinoid Agonists Stimulate [³H]GABA Release in the Globus Pallidus of the Rat When G_iProtein-Receptor Coupling Is Restricted: Role of Dopamine D2 Receptors

González¹,

Paz²,

Florán³

et al. 2008

J Pharmacol Exp Ther

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“…CP55940 decreased the high and low K d affinities for dopamine (a function of the receptor-G protein interaction) in equilibrium binding assays of D 2 receptors in rat striatal membranes . Cannabinoid and D 2 agonists converged to inhibit forskolin-activated adenylyl cyclase as a subadditive response in rodent and monkey striatal membranes (Meschler and Howlett, 2001). In cultured striatal cells, costimulation by dopaminergic and cannabinoid agonists converted the response from a G imediated inhibition to a G s -mediated stimulation of cAMP production (Glass and Felder, 1997).…”

Section: Cb 1 Receptor Homomers and Heteromersmentioning

confidence: 99%

“…Observations of cannabinoid-stimulated protein kinase A activation suggests that cAMP production is a viable signaling mechanism in basal ganglia (Andersson et al, 2005;Borgkvist et al, 2008). However, caution should be observed in interpreting in vivo data, in that D 1 dopamine (Bidaut Russell and Howlett, 1991;Meschler and Howlett, 2001) and A 2A adenosine receptors (Carriba et al, 2007Marcellino et al, 2008) might contribute as components of a heteromeric complex. Immunocytochemical studies suggest that coexpression of CB 1 and D 2 receptors occurs on the output neurons of the olfactory tubercle, striatum, hippocampus, or neocortex (Hermann et al, 2002).…”

Section: Cb 1 Receptor Homomers and Heteromersmentioning

confidence: 99%

International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid Receptors and Their Ligands: Beyond CB₁and CB₂

Howlett²,

et al. 2010

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“…Thus, CB1 receptors and dopamine D2 receptors are expressed on the same neuronal elements. Individually, both CB1 and D2 receptor agonists inhibit forskolin-stimulated adenylyl cyclase activity in a convergent signal transduction pathway (Meschler and Howlett, 2001). However, these two receptors were found to display a complex signaling interaction in primary striatal neuron cultures (Glass and Felder, 1997).…”

mentioning

confidence: 99%

Concurrent Stimulation of Cannabinoid CB1 and Dopamine D2 Receptors Enhances Heterodimer Formation: A Mechanism for Receptor Cross-Talk?

Kearn

Blake-Palmer²,

Daniel³

et al. 2005

Molecular Pharmacology

320

271

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Dopamine and endogenous cannabinoids display complex interactions in the basal ganglia. One possible level of interaction is between CB1 cannabinoid and D2 dopamine receptors. Here, we demonstrate that a regulated association of CB1 and D2 receptors profoundly alters CB1 signaling. This provides the first evidence that CB1/D2 receptor complexes exist, are dynamic, and are agonist-regulated with highest complex levels detected when both receptors are stimulated with subsaturating concentrations of agonist. The consequence of this interaction is a differential preference for signaling through a "nonpreferred" G protein. In this case, D2 receptor activation, simultaneously with CB1 receptor stimulation, results in the receptor complex coupling to G␣s protein in preference to the expected G␣i/o proteins. The result of this interaction is an increase in the second messenger cAMP, reversing an initial synergistic inhibition of adenylyl cyclase activity seen at subthreshold concentrations of cannabinoid agonist. Additionally, a pertussis toxin insensitive component in the activation of extracellular signal-regulated kinase (ERK) 1/2 kinases by the cannabinoid agonist CP 55,940 [(1R,3R,4R)-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-4-(3-hydroxypropyl)cyclohexan-1-ol] is revealed in cells stably expressing both CB1 and D2 receptors. Thus, concurrent receptor stimulation promotes a heterooligomeric receptor complex and an apparent shift of CB1 signaling from a pertussis toxin-sensitive inhibition to a partly pertussis toxin-insensitive stimulation of adenylyl cyclase and ERK 1/2 phosphorylation.

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Signal transduction interactions between CB1 cannabinoid and dopamine receptors in the rat and monkey striatum

Cited by 96 publications

References 31 publications

Cannabinoid Agonists Stimulate [³H]GABA Release in the Globus Pallidus of the Rat When G_iProtein-Receptor Coupling Is Restricted: Role of Dopamine D2 Receptors

Cannabinoid Agonists Stimulate [³H]GABA Release in the Globus Pallidus of the Rat When G_iProtein-Receptor Coupling Is Restricted: Role of Dopamine D2 Receptors

International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid Receptors and Their Ligands: Beyond CB₁and CB₂

Concurrent Stimulation of Cannabinoid CB1 and Dopamine D2 Receptors Enhances Heterodimer Formation: A Mechanism for Receptor Cross-Talk?

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Signal transduction interactions between CB1 cannabinoid and dopamine receptors in the rat and monkey striatum

Cited by 96 publications

References 31 publications

Cannabinoid Agonists Stimulate [3H]GABA Release in the Globus Pallidus of the Rat When GiProtein-Receptor Coupling Is Restricted: Role of Dopamine D2 Receptors

Cannabinoid Agonists Stimulate [3H]GABA Release in the Globus Pallidus of the Rat When GiProtein-Receptor Coupling Is Restricted: Role of Dopamine D2 Receptors

International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid Receptors and Their Ligands: Beyond CB1and CB2

Concurrent Stimulation of Cannabinoid CB1 and Dopamine D2 Receptors Enhances Heterodimer Formation: A Mechanism for Receptor Cross-Talk?

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Cannabinoid Agonists Stimulate [³H]GABA Release in the Globus Pallidus of the Rat When G_iProtein-Receptor Coupling Is Restricted: Role of Dopamine D2 Receptors

Cannabinoid Agonists Stimulate [³H]GABA Release in the Globus Pallidus of the Rat When G_iProtein-Receptor Coupling Is Restricted: Role of Dopamine D2 Receptors

International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid Receptors and Their Ligands: Beyond CB₁and CB₂