Striatal CB1 and D2 receptors regulate expression of each other, CRIP1A and δ opioid systems.
J Neurochem
; 124(6): 808-20, 2013 Mar.
Article
en En
| MEDLINE
| ID: mdl-23286559
ABSTRACT
Although biochemical and physiological evidence suggests a strong interaction between striatal CB1 cannabinoid (CB1 R) and D2 dopamine (D2 R) receptors, the mechanisms are poorly understood. We targeted medium spiny neurons of the indirect pathway using shRNA to knockdown either CB1 R or D2 R. Chronic reduction in either receptor resulted in deficits in gene and protein expression for the alternative receptor and concomitantly increased expression of the cannabinoid receptor interacting protein 1a (CRIP1a), suggesting a novel role for CRIP1a in dopaminergic systems. Both CB1 R and D2 R knockdown reduced striatal dopaminergic-stimulated [(35) S]GTPγS binding, and D2 R knockdown reduced pallidal WIN55212-2-stimulated [(35) S]GTPγS binding. Decreased D2 R and CB1 R activity was associated with decreased striatal phosphoERK. A decrease in mRNA for opioid peptide precursors pDYN and pENK accompanied knockdown of CB1 Rs or D2 Rs, and over-expression of CRIP1a. Down-regulation in opioid peptide mRNAs was followed in time by increased DOR1 but not MOR1 expression, leading to increased [D-Pen2, D-Pen5]-enkephalin-stimulated [(35) S]GTPγS binding in the striatum. We conclude that mechanisms intrinsic to striatal medium spiny neurons or extrinsic via the indirect pathway adjust for changes in CB1 R or D2 R levels by modifying the expression and signaling capabilities of the alternative receptor as well as CRIP1a and the DELTA opioid system.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Portadoras
/
Receptores de Dopamina D2
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Receptores Opioides delta
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Cuerpo Estriado
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Receptor Cannabinoide CB1
Límite:
Animals
Idioma:
En
Revista:
J Neurochem
Año:
2013
Tipo del documento:
Article
País de afiliación:
Estados Unidos