Dopamine D ₁ and adenosine A ₁ receptors form functionally interacting heteromeric complexes

Abstract

During the 1980s, indications for the existence of intramembrane interactions between different G protein-coupled receptors, mainly between neuropeptide and monoamine receptors, were obtained in several brain areas (1, 2). It was later proposed that a possible molecular mechanism for this phenomenon was receptor heteromerization (3) and direct evidence for homo-and heteromerization of G protein-coupled receptors has been obtained by several groups. It was first shown that serotonin 5-HT-1B receptors exist as monomers and dimers (4). This was followed by demonstration of dimers and oligomers of dopamine D 1 and D 2 receptors (D 1 and D 2 R) in transfected Sf cells (5-7) and of adenosine A 1 receptors (A 1 Rs) in a natural cell line and in mammalian brain (8). It has recently been reported that a fully functional ␥-aminobutyric acid (GABA) type B receptor demands the heterodimerization of GABA B R1 and GABA B R2 receptors (9-12). Moreover, two functional opioid receptors, the and ␦ subtypes, can undergo heteromerization, which changes the pharmacology of the individual receptors and potentiates signal transduction (13). Finally, D 2 R and somatostatin receptor subtype 5 have been shown to physically interact by forming heterooligomers with enhanced functional activity (14). Direct protein-protein coupling can also exist between G proteincoupled anion channel receptors, as recently shown for dopamine D5 receptor and GABA A receptor, making possible bilateral inhibitory interactions between these receptors (15).Antagonistic adenosine͞dopamine interactions have been widely reported in the central nervous system in behavioral and biochemical studies. Furthermore, in animal models, adenosine agonists and antagonists are potent atypical neuroleptics and antiparkinsonian drugs, respectively (16-18). Thus, adenosine agonists inhibit and adenosine antagonists, such as caffeine, potentiate the behavioral effects induced by dopamine agonists. The evidence suggests that this antagonism is at least in part caused by an intramembrane interaction between specific subtypes of dopamine and adenosine receptors, namely, between

Regulation of Dopamine D1 Receptor Trafficking and Desensitization by Oligomerization with Glutamate N-Methyl-D-aspartate Receptors

“…1A shows the results from Western blot analysis performed with different tissue fractions with antibodies recognizing the D 1 receptor, the NR1 subunit, ␣-Ca 2ϩ /calmodulindependent protein kinase II, and protein kinase C⑀. As previously reported (28), immunoreaction with the anti-D 1 receptor antibody revealed a major specific band of ϳ50 kDa. This species was detectable in all tissue fractions, but was enriched in the PSD fraction.…”

Dopaminergic signaling in dendritic spines

“…Besides short peptide sequences involved in G protein and arrestin binding, the remaining portions of these intracellular domains are presumably free to interact with other proteins. Using approaches such as co-immunoprecipitation and the yeast two-hybrid system, an increasing number of DRIPs are being identified [41][42][43]53,[68][69][70][71][72][73][74][75][76][77][78][79][80][81][82][83]. The confirmed DRIPs and their suggested functions are summarized in Table 1.…”

神经细胞中多巴胺d1和d5受体不同亚细胞分布和胞内转运的特性

“…The heterodimerization of different GPCRs can result in the modulation of their function and/or the redistribution of their subcellular locations [17][18][19][20] . It was documented that 2-adrenergic agonist isoproterenol could induce the internalization of opioid receptors through the hetero-dimer of 2-adrenergic receptor and opioid receptor [20] .…”

“…Several lines of evidence raise the possibility of the hetero-dimerization between D1R and mAChR: (1) In NG108-15 cells, the endogenous mAChR was reported to be internalized by ACh stimulation [37] , and the mAChR could form heterodimer with other GPCRs [38] . (2) D1R could also form the heterodimer with other GPCRs and mutually regulate each other, just like the heterodimer between D1R and adenosine A1 receptor [18] . (3) D1R and mAChR were found to co-localize in striatonigral neurons both in vivo [39,40] and in our expression system.…”

“…3D), which indicated no translocation of D5R-YFP by the drug pretreatment. 3.4 D1R and D5R co-expressed in the same cell kept their distinct trafficking properties Dopamine D1 receptors can not only form the homodimer [16,17] , but also form the heterodimer with other GPCRs [17,18] . The heterodimerized GPCRs can result in the mutual modulation of their function and/or the redistribution of their subcellular locations [17][18][19][20] .…”