Our work involves the study of genes encoding receptors that bind the neurotransmitters acetylcholine, dopamine, and glutamate. Previous work led to the molecular cloning, sequencing and expression of a family of muscarinic acetylcholine receptor subtype genes. We have continued to characterize these subtypes pharmacologically with regard to agonists and antagonists, anatomic distribution, their selectivity of coupling to G-proteins, second messengers and ion channels, and the development of antibodies specific for each protein subtype. Using the recently reported sequence of a rat cDNA that encodes a dopamine D2 receptor, we have mapped the distribution of the corresponding mRNA in rat retina and brain, and have cloned, sequenced and expressed a cDNA that encodes the human homolog of this receptor and likewise a human dopamine D1 receptor. This work has provided evidence that dopamine receptors, like muscarinic receptors, may be derived from a family of genes. We are attempting to clone the other members of the family, and to study the selectivity of coupling of the cloned dopamine receptors to G-proteins, second messengers, and ion channels. Finally, sequences of the rat cDNAs that encode neuronal nicotinic acetycholine receptors have been reported, and we have cloned some of the human homologs of these receptors. Because of a hypothetical evolutionary similarity between glutamate and nicotinic acetylcholine receptors, we have been attempting to clone the glutamate receptors by homology cloning. As a result, we recently cloned, sequenced and expressed the human homolog of the rat glutamate receptor.
