Concurrent stimulation of cannabinoid CB1 and dopamine D2 receptors enhances heterodimer formation: a mechanism for receptor cross-talk?
| Autor: | Ken Mackie, Katherine Blake-Palmer, Emma Daniel, Christopher S. Kearn, Michelle Glass |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
medicine.medical_specialty
Receptor complex Quinpirole medicine.medical_treatment Biology Cell Line Receptor Cannabinoid CB1 Internal medicine Dopamine receptor D2 Dopamine receptor D5 medicine Cannabinoid receptor type 2 Humans G protein-coupled receptor Pharmacology Dose-Response Relationship Drug Receptors Dopamine D2 Receptor Cross-Talk Cell biology Endocrinology Molecular Medicine GPR18 lipids (amino acids peptides and proteins) Cannabinoid Dimerization Endogenous agonist |
| Zdroj: | Molecular pharmacology. 67(5) |
| ISSN: | 0026-895X |
| Popis: | 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 alpha s protein in preference to the expected G alpha 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. |
| Databáze: | OpenAIRE |
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