Traditionally, the interaction of G protein-coupled receptors has been described by models that assume that the receptor exists as a monomer coupled to G protein in a 1:1 stoichiometry. However, these classical models of receptor/G protein coupling may be oversimplified. It has now been shown that many G protein-coupled receptors can form dimers or higher order oligomers and that this phenomenon has relevance to receptor function (for a review, see Ref. 6). Dopamine receptors have also been shown to form dimers and higher order oligomers. Evidence has been provided for D 1 , D 2 , and D 3 homodimers in transfected cell lines (7-9), and D 2 receptors have been shown to exist as dimers in human and rat brain tissues (10). Moreover, Rocheville et al. (11) have recently shown that the dopamine D 2 receptors not only form homodimers but also form heterodimers with somatostatin SSTR 5 receptors. In addition, Gines et al. (12) have shown that the dopamine D 1 receptor forms hetero-oligomers with the adenosine A 1 receptor.As the issue of G protein-coupled receptor homo-and heterodimerization is becoming more and more important, it is crucial to define the mechanism(s) of receptor-receptor interactions in order to predict which receptors can interact with one another. The results obtained until now suggest that more than one mechanism exists and that one receptor can interact with another in more than one way.One of the mechanisms that have been proposed to explain receptor dimerization is the phenomenon of domain swapping
Objectives-To determine whether continous waking day dopaminergic stimulation with the dopamine agonist apomorphine can reduce levodopa induced dyskinesias in Parkinson's disease Methods-19 patients with severe unpredictable refractory motor fluctuations and functionally disabling levodopa induced dyskinesias were treated with continuous subcutaneoius apomorphine monotherapy for a minimum duration of 2.7 years Results-A mean 65% reduction in dyskinetic severity and a mean 85% reduction in frequency and duration occurred. On discontinuing levodopa a concomitant reduction in oV period time was also seen (35% of waking day "oV" reduced to 10%) Conclusion-Continuous waking day dopaminergic stimulation with apomorphine reset the threshold for dyskinesias and led to a pronounced reduction in their frequency. Apomorphine should be considered as a less invasive alternative to pallidotomy or deep cerebral stimulation in controlling levodopa induced interdose dose dyskinesias. (J Neurol Neurosurg Psychiatry 1998;64:573-576)
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