Dopamine D4 receptors: curiouser and curiouser.

Identification of the D, receptor The D4 receptor was fit identified, using molecular biological techniques, from human’ and from rat2 and shown to be a member of the family of G protein-coupled dopamine receptors. It has substantial homology with Dz and DJ receptors (and is a member of the D,-like receptor subfamily) but its distribution and pharmacological properties are different from either of these receptors. When the distribution of mRNA for the D, receptor was mapped in the rat and monkeyiJ, it was found to be present in the brain at low levels in several limbic and cortical regions with relatively lower levels in the basal ganglia. Unexpectedly, significant levels of mRNA for the Dj receptor were also found in the heart2 and retinas. However, the level of mRNA may not directly reflect the level of receptor protein that is expressed, and preliminary measurements in human brain4 indicate higher levels of D, receptors than would be predicted from the mRNA levels in the rat. Preliminary determination of the mRNA levels in human brain does, however, support the idea that the D, receptor may be present at higher levels than in rat, and has shown that mRNA for this receptor is present in the retina, hypothalamus, mesencephalon, cortex and pituitary’. The presence of the D4 receptor in certain limbic and cortical brain regions and its relative absence from striatal regions suggests that D4 receptorselective antagonists might act as novel antipsychotic drugs with reduced extrapyramidal side-effects.