Interaction of adenosine receptors with other receptors from therapeutic perspective in Parkinson's disease.

Altered dopaminergic neurotransmission in the basal ganglia is observed in Parkinson's disease (PD) and L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesias (LID). An attractive alternative for treating LID is to use adjunct drugs to modulate nondopaminergic neurotransmitter systems in the basal ganglia. For example, adenosine receptors have received attention over the past years for the treatment of PD and LID. Adenosine interacts closely with dopamine and plays an important role in the function of striatal GABAergic efferent neurons. Excitatory glutamatergic neurotransmission is also modulated by adenosine in the striatum. Hence, based on the unique cellular and regional distribution of this system, adenosine neurotransmission could have an important implication for the development of new therapeutic strategies targeting the basal ganglia disorders. Indeed, A2A adenosine receptor antagonists were shown to improve motor deficits in PD and to reduce the severity of LID. A2A receptor subtypes are selectively found on striatopallidal neurons and can couple with receptors of interest in PD, such as D2 dopamine and metabotropic glutamate receptor type 5 (mGlu5) receptors, and form functional heteromeric complexes. This chapter will review relevant studies investigating the role and contribution of adenosine receptor subtypes in pathophysiology of PD and LID. The interactions of adenosine receptors, especially A1 and A2A receptor subtypes, with other receptors implicated in the pathophysiology of PD and LID such as dopaminergic and glutamatergic receptors will be reviewed. The implication of these interactions in the development and expression of PD symptoms and LID needs further investigation to find novel drug targets.