Dopamine D1-histamine H3 receptor heteromers provide a selective link to MAPK signaling in GABAergic neurons of the direct striatal pathway.
J Biol Chem
; 286(7): 5846-54, 2011 Feb 18.
Article
em En
| MEDLINE
| ID: mdl-21173143
ABSTRACT
Previously, using artificial cell systems, we identified receptor heteromers between the dopamine D(1) or D(2) receptors and the histamine H(3) receptor. In addition, we demonstrated two biochemical characteristics of the dopamine D(1) receptor-histamine H(3) receptor heteromer. We have now extended this work to show the dopamine D(1) receptor-histamine H(3) receptor heteromer exists in the brain and serves to provide a novel link between the MAPK pathway and the GABAergic neurons in the direct striatal efferent pathway. Using the biochemical characteristics identified previously, we found that the ability of H(3) receptor activation to stimulate p44 and p42 extracellular signal-regulated MAPK (ERK 1/2) phosphorylation was only observed in striatal slices of mice expressing D(1) receptors but not in D(1) receptor-deficient mice. On the other hand, the ability of both D(1) and H(3) receptor antagonists to block MAPK activation induced by either D(1) or H(3) receptor agonists was also found in striatal slices. Taken together, these data indicate the occurrence of D(1)-H(3) receptor complexes in the striatum and, more importantly, that H(3) receptor agonist-induced ERK 1/2 phosphorylation in striatal slices is mediated by D(1)-H(3) receptor heteromers. Moreover, H(3) receptor-mediated phospho-ERK 1/2 labeling co-distributed with D(1) receptor-containing but not with D(2) receptor-containing striatal neurons. These results indicate that D(1)-H(3) receptor heteromers work as processors integrating dopamine- and histamine-related signals involved in controlling the function of striatal neurons of the direct striatal pathway.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Dopamina
/
Histamina
/
Receptores de Dopamina D1
/
Receptores Histamínicos H3
/
Corpo Estriado
/
Sistema de Sinalização das MAP Quinases
/
Neurônios
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article