Polypeptides with a dopaminergic receptor (D2-R and D3-R) activity and use of these polypeptides to screen substances having a selective activity on these polypeptides

摘要

The new polypeptides have a defined of 446 amino acids or comprise fragments of it; provided the fragments; (i) contain at least those sites necessary for, when the fragment is exposed at the surface of a cell, binding to its (ant)agonists, specifically and in a measurable way (e.g. by means of a radioative ligand); (ii) can be recognised by Abs which recognise the full sequence but not dopaminergic D1 or D2 receptors; or (iii) can generate Abs recognising the full sequence but not dopaminergic receptor D1 or D2. The polypeptides include variants having licalised mutations provided they have not lost their dopaminergic receptor properties. Preferrred polypeptides show agonist affinity, by competition with the ligand iodosulphide-1 125, in the order quinpirole greater than apomorphine = dopamine and antagonist activity in the order raclopiriae greater than UH232 = haloperidol. DNA encoding the polypeptides, recombinant vectors and transformed hosts are also claimed. Antibodies to the peptides and nucleotide probes are claimed. Also claimed are diagnostic methods and kits specifically for pathologic expression of dopaminergic D3 receptor and genetic abnormalities of D3 receptor (in vitro).