| Abstract No.: | C-B3055 |
| Country: | Canada |
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| Title: | RECEPTOR AND REGION SPECIFIC COLOCALIZATION AND FUNCTIONAL INTERACTION OF DOPAMINE RECEPTORS 1-5 WITH DARPP-32 IN RAT BRAIN AND CULTURED STRIATAL NEURONS |
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| Authors/Affiliations: | 1 Padmesh Singh Rajput*; 1 Geetanjali Kharmate; 1 Rishi Somvanshi; 1 Ujendra Kumar;
1 University of British Columbia, Vancouver, BC, Canada
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| Content: | Introduction- Dopamine (DA) a major brain neurotransmitter regulates motor activity, cognition, emotion and positive reinforcement. DA-containing neurons located in the substantia nigra project to the dorsal and ventral striatum. Dysfunction of dopaminergic system involves Parkinson’s disease, depression and schizophrenia. The actions of DA are mediated via five receptor subtypes divided into two subclasses – D1-like (D1R, D5R) and D2-like (D2R, D3R, D4R) which regulate adenylyl cyclase. In the central nervous system target for the DA action is dopamine and cyclic AMP-regulated phosphoprotein (DARPP-32) that is activated via the dopamine receptors. DARPP-32 like immunoreactivity is mostly confined to the projection neurons in striatum and cortical neurons which are susceptible in excitotoxicity. Whether DRs functionally interact with DARPP-32 is not well understood.
Materials and Methods- In the present study using indirect immunofluorescence immunocytochemistry we mapped the coexpression of D1R-D5R with DARPP-32 in rat brain and cultured striatal neurons. Additionally, we employed biophysical method ‘pbFRET’ to determine whether DR subtypes functionally interact with DARPP-32. Results- We observed three different neuronal population either expressing DRs or DARPP-32 alone or colocalization. In cortex as well as striatum D2R is one of the most predominant subtypes colocalized with DARPP-32 and followed by D3R, D4R, D1R and D5R. Most significantly pbFRET analysis revealed that D1R, D2R and D4R functionally interact with DARPP-32 in cultured striatal neurons. Conclusion- Taken together these results provide the evidence for colocalization of DARPP-32 with DRs in receptor and region specific manner in-vivo as well as in-vitro, such distinct distributional pattern can be used as an index about the role of DRs subtypes in excitotoxicity. In conclusion our FRET data suggest that activation of D1R and D2R subtype may participate in modulation of signaling pathway whereas D4R might function in a concert with DARPP-32 on the role of antipsychotic drugs in Schizophrenia and involve in modulation of phosphorylation. |
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