Characterization of a novel D2‐like dopamine receptor with a truncated splice variant and a D1‐like dopamine receptor unique to invertebrates from Caenorhabditis elegans

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Abstract
We have cloned two novel Caenorhabditis elegans dopamine receptors, DOP‐3 and DOP‐4. DOP‐3 shows high sequence homology with other D2‐like dopamine receptors. As a result of alternative splicing, a truncated splice variant of DOP‐3, DOP‐3nf, was produced. Because of the in‐frame insertion of a stop codon in the third intracellular loop, DOP‐3nf lacks the sixth and seventh transmembrane domains that are found in the full‐length DOP‐3 receptor. Reporter gene assay showed that DOP‐3 attenuates forskolin‐stimulated cAMP formation in response to dopamine stimulation, whereas DOP‐3nf does not. When DOP‐3 was coexpressed with DOP‐3nf, the ability to inhibit forskolin‐stimulated cAMP formation was reduced. DOP‐4 shows high sequence homology with D1‐like dopamine receptors unique to invertebrates, which are distinct from mammalian D1‐like dopamine receptors. Reporter gene assay showed that DOP‐4 stimulates cAMP accumulation in response to dopamine stimulation. These two receptors provide new opportunities to understand dopaminergic signaling at the molecular level.

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