Dopamine D2 receptor dimers and receptor-blocking peptides
- PMID: 8858125
- DOI: 10.1006/bbrc.1996.1489
Dopamine D2 receptor dimers and receptor-blocking peptides
Abstract
Dopamine D2 receptors exist as dimers in whole cell lysate, crude membranes prepared from human caudate, and following solubilization and immunoprecipitation of the receptor from these tissues. Photoaffinity labelling experiments confirmed that D2 receptors exist either as monomers that are selective targets for spiperone or as dimers that are targets for nemonapride. Incubation of D2 dimers with peptides derived from the putative transmembrane (TM) domains of the D2 receptor, or incubation under high temperatures or low pH resulted in the dissociation of the dimer to monomer. D2-TM peptides were unable to dissociate dopamine D1 and serotonin 5-HT1B receptor dimers, suggesting that receptor dimers are formed by specific intermolecular noncovalent interactions involving TM regions. This opens a path to new selective therapeutic receptor-blocking compounds based on this principle of mimicking transmembrane portions of neurotransmitter receptors.
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