Original articlesEvidence for Adenosine/Dopamine Receptor Interactions: Indications for Heteromerization
Section snippets
Dopamine-adenosine interactions in the central nervous system
Adenosine is an endogenous nucleoside acting as a neuromodulator in the central nervous system. Its actions are mediated by adenosine receptors, four of which have been cloned and pharmacologically characterized: A1, A2A, A2B and A3 (Fredholm et al. 1994). Among those four subtypes A1 and A2A are the main targets of the behavioral effects occurring in animals treated with adenosine analogs Ferré et al. 1992, Ferré et al. 1993, Ferré et al. 1997, Fredholm 1995. Caffeine, as an example of an
Adenosine receptors as a model for homomeric and heteromeric protein–protein interactions
The work of Franco and colleagues on A1 adenosine receptors has provided a better understanding of how ligand binding and signal transduction is affected by homotypic and heterotypic protein–protein interactions Franco et al. 1996, Franco et al. 1997, Ginés et al. 2000, Sarrió et al. 2000.
The binding of [3H]-2-chloroadenosine to A1 receptors present in rat brain membranes was first studied in two laboratories. Basically, depending upon the absence or presence of exogenous adenosine deaminase
Dimers and clusters of gpcrs
Since the description of the existence of homodimers for 5HT1B, D1, D2 (Ng et al. 1993, Ng et al. 1994a, Ng et al. 1994b, 1995) and A1 receptors (Ciruela et al. 1995) a number of reports have described the occurrence of homodimers for a variety of GPCRs. In fact it now seems that any member of the GPCR superfamily can be present in form of dimers in the plasma membrane. To our knowledge reports on the existence of dimers have been disclosed for dopamine (Ng et al. 1993, Ng et al. 1994a, Ng et
Dopamine-adenosine receptor– receptor interactions
Some of the functional interactions between dopamine and adenosine can be explained by downstream interactions. Thus the A1/D1 receptor antagonism at the level of the cAMP formation can be easily explained by the fact that G-proteins for A1R and D1R are differently coupled to adenylate cyclase. However, some of the functional interactions occur even in acute treatments (see above) which suggested that a direct interaction may occur. Due to the occurrence of homodimers of adenosine and of
Homo- and heteromerization of gpcr: understanding the nervous system
In 1999 the first reports on heteromerization involving GPCR started to appear in the literature. They corresponded to heterodimerization among receptors for the same ligand. Heterodimers consisting of two subtypes of opioid receptors (κ and δ) have a pharmacological profile that differs from that corresponding to each of the receptor subtypes when expressed alone (Jordan and Devi 1999). The case of heterodimerization of GABABR1 and GABABR2 receptors is paradigmatic since cells only express
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