Diversity of dopamine receptors: new molecular and pharmacological developments.
Five distinct dopamine (DA) receptors, named D1-D5, are expressed in the central nervous system where they control motor function, emotional states, and endocrine physiology. With the production of receptor-specific knockout mice and the development of receptor subtype specific ligands, our understanding of dopaminergic systems in the brain is expanding rapidly. In some of the more recent developments, the D4R has been shown to be activated by all three catecholamine neurotransmitters: DA, epinephrine, and norepinephrine. This functional activation by multiple neurotransmitters provides a novel mechanism for integration of catecholamine signaling. In addition, the D4R was reported last year to show genetic linkage to a personality trait called novelty seeking, and now has been implicated in the manifestation of attention deficit hyperactivity disorder, which affects 3-6% of school age children. New evidence has emerged indicating that yet another DA receptor subtype may exist which has D1-like pharmacology but couples to phosphoinositol turnover, which may be of particular importance in the light of recent studies which show decreased D1-like receptor density in brain from schizophrenic patients. This review will cover these and other new developments in the area of DA receptors which have important implications for the understanding of human behavior and disease.
Hartman
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Pharmaceuticals Division, Hoffmann-La Roche, Basel, Switzerland.
Lanau
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D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D011954:Receptors, Dopamine / Q000145:classification / Q000187:drug effects / Q000502:physiology; D017447:Receptors, Dopamine D1 / Q000235:genetics / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D050638:Receptors, Dopamine D4; D012559:Schizophrenia / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
D018076:DNA, Complementary; C493599:DRD4 protein, human; D015259:Dopamine Agents; C493600:Drd4 protein, mouse; D018377:Neurotransmitter Agents; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4