The rat dopamine D4 receptor: sequence, gene structure, and demonstration of expression in the cardiovascular system

Dopamine receptors have been implicated in a variety of neurological and neuropsychiatric disorders. Here we describe the use of the polymerase chain reaction and low stringency library screening to isolate a rat genomic clone encoding a novel dopamine receptor. Sequence data and pharmacological analysis reveal this clone to be the rat analog of the human D4 receptor, which exhibits a high affinity for the antipsychotic drug clozapine. The mRNA for this receptor shows a restricted pattern of expression in the central nervous system. Significant levels of expression were found in the hypothalamus, thalamus, olfactory bulb, and frontal cortex. However, 20-fold higher levels of D4 mRNA expression were observed in the cardiovascular system. Thus, this receptor appears to mediate dopamine function in the cardiovascular system as well as the central nervous system.