Heteromerization of Adenosine and Dopamine Receptor Subtypes: Relevance for Neuronal Integration in Normal and Pathological States
Ever since the beginning of the 1980’s indications have been obtained for the existence of intramembrane receptors-receptor interactions among different types of G protein coupled receptors (GPCR) in the brain (Agnati et al., 1982, Fuxe et al., 1983) and it was suggested in 1993 that the structural basis for these intramembrane interactions is represented by the formation of GPCR heterodimers (Zoli et al., 1993). It must also be noticed that already in the early 80’s crosslinking and radiation inactivation experiments and experiments on gel filtration and analytical sucrose density gradient ultracentrifugation indicated that GPCR could exist as homodimers (see Salahpour et al., 2000). There now exists strong evidence for homo- and heteromerization of GPCR from several groups (see, e.g., Salahpour et al., 2000, Bouvier 2001, Devi and Brady 2000, Tallman 2000, Franco et al., 2000), including evidence for the existence of dimers and oligomers of D1 and D2 receptors and of A1 receptors (Ciruela et al., 1995). In the present review the evidence for adenosine and dopamine receptor subtype-specific heteromerizations will be presented and their role in mediating A1/D1 and A2A/D2 antagonistic receptor interactions and in receptor trafficking will be discussed (Gines et al., 2000, Hillion et al., 2001).
KeywordsHeteromeric Complex Gaba Pathway Heteromeric Receptor Complex Volume Transmission Signal Striatal Membrane Preparation
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