The Canadian Journal of Neurological Sciences

The neuroleptic/dopamine receptor, with its picomolar affinity for potent neuroleptics, is the functional dopamine receptor of the brain. This receptor has been termed the D2 dopamine receptor, and it inhibits or interferes with dopamine-stimulated adenylate cyclase. This D2 receptor has two states, each having different affinity for dopamine. The high-affinity state, termed D2 hlg , has a 10 nM affinity for dopamine and is the functional correlate for dopamine autoreceptors and for the dopamine receptor in the pituitary gland. The low-affinity state, termed D2' , has a 2000 nM affinity for dopamine, and may possibly represent the desensitized state of the dopamine receptor or the functional post-synaptic receptor. RESUME: Le recepteur neuroleptique/dopamine, avec son affmite picomolaire pour les neuroleptiques puissants, est le recepteur dopaminergique fonctionnel du cerveau. Ce recepteur fut appele le recepteur dopaminergique D2; il inhibe ou interfere avec l'adenylate cyclase stimulee par la dopamine. Ce recepteur D2 , a une affmite a 10 nM pour la dopamine et correspond a l'etat fonctionnel des autorecepteurs dopaminergiques et des recepteurs dopaminergiques de la glande pituitaire. L'etat de basse affmite, D2 , a une affmite a 2000 nM pour la dopamine, et represente probablement l'etat desensibilise du recepteur dopaminergique. Can. J. Neurol. Sci. 1984; 11:108-113 Dopamine receptors occur in high density in the putamen and caudate nucleus with densities of about 11 pmoles of receptors per gram of tissue. Progressively lower densities are found in the globus pallidus, the substantia nigra, the median eminence and anterior pituitary gland, the area postrema, the ventral tegmental region, the retina, and the paraolfactory cortex (see List and Seeman, 1981 for further Refs.). Although dopamine receptors were first detected about 10 years ago (Seeman et al., 1974, 1975a, b), the conditions for measuring their precise absolute concentrations in different brain regions are still being developed (Seeman et al., 1982). Definition of a dopamine receptor A neurotransmitter receptor is a membrane-located protein which when stimulated by the transmitter results in an electrical or chemical effect. A receptor should be affected by drug doses or concentrations which correlate with the drug doses or concentrations causing a particular brain response subserved by that receptor. A dopamine receptor is defined as that receptor which is more sensitive to dopamine than to any other neurotransmitter. Thus, the primary criterion of a dopamine receptor is that it be most sensitive to dopamine, less sensitive to noradrenaline and even less sensitive to serotonin. If one includes exogenous drugs, such as bromocriptine, apomorphine and ADTN (6, 7-dihydroxy-2-aminotetralin), a dopamine receptor is defined as one which has the following rank order of dopaminergic agonist potencies: Bromocriptine > apomorphine = ADTN > dopamine > noradrenaline > serotonin A dopamine receptor and a "dopaminergic site" generally have the same rank order of sensitivities to dopamine agonists; a dopamine receptor, however, has a functional correlate, while the functional correlate of a "dopaminergic site" is one which rejnains to be established. Classification of central and peripheral dopaminergic sites and receptors Subclassification of the dopaminergic sites (and/or states) depends on the absolute molarities of agonists and antagonists to which the sites are sensitive. Thus, the nomenclature used in this laboratory is based solely on the absolute sensitivities of the site to three drugs: dopamine, spiperone and sulpiride. This is summarized in Table I and Fig. I. The sites and/or states (in Table 1) are defined according to two criteria: A) by the order of magnitude of the absolute molarities (uM or nM) of dopamine and spiperone that were 50% effective in vitro; and B) by whether or not the site was sensitive to R-sulpiride of S-sulpiride. Dopamine-stimulated adenylate cyclase, or the D, site: Dopamine-stimulated adenylate cyclase, first detected in 1972 by Kebabian et al., has been termed the D| site (Kebabian and Calne, 1979). The Dt site is sensitive to micromolar concentrations of dopamine as well as to micromolar concentrations of spiperone, Table 1: Definitions of Dopaminergic Dopamine Cjo Spiperone IC5( Sulpiridesensitive? D, u.M