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Published on: June 5, 2017
Diversity and bias through dopamine D2R heteroreceptor complexes
Dasiel O Borroto-Escuela1, Kjell Fuxe2
1Department of Neuroscience, Karolinska Institutet, Retzius väg 8, 17177 Stockholm, Sweden; Department of Biomolecular Science, Section of Physiology, University of Urbino, Campus Scientifico Enrico Mattei, via Ca' le Suore 2, I-61029 Urbino, Italy; Observatorio Cubano de Neurociencias, Grupo Bohío-Estudio, Zayas 50, 62100 Yaguajay, Cuba.
Abstract:
The D2R is a hub receptor interacting with a large number of other GPCRs. A2AR activation of the antagonistic A2AR-D2R interaction not only leads to inhibition of the Gi/o signaling but also to an increase in β-arrestin2 signaling over the D2R protomer. Hallucinogenic 5-HT2AR agonists can produce a biased agonist state at the 5-HT2AR protomer of D2R-5-HT2AR heteroreceptor complexes with increased D2R recognition and Gi/o mediated signaling. Allosteric receptor-receptor interactions in D2-NTR1 heteroreceptor complexes inhibit D2R function and can switch G protein coupling. These large numbers of D2R heterocomplexes and their allosteric receptor-receptor interactions produce a marked increase in diversity and bias of the participating D2R protomers opening a promised land for drug development in schizophrenia, addiction and Parkinson's disease.
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