Subtypes of dopamine receptors

The physiological actions of DA are mediated by at least five different G protein-coupled receptor subtypes, which are classified into Dj-like family (D, and D5) and D2-like family (D2, D3 and D4). The first identification of different DA receptor subtypes was made by Spano et al. (1978). Thereafter two receptor subtypes, named D, and D2, were classified on the basis of their stimulatory or inhibitory activity on adenylyl cyclase (Kebabian and Caine, 1979). 

After the introduction of gene cloning methodologies, three new receptor subtypes, D3, D4 and D5, were characterized over the years. Characterization of complementary DNA for all five receptor subtypes showed that D3 and D5 receptors share high homology in their transmembrane sequences similarly, the transmembrane sequences of D2, D3 and D4 receptors are conserved in the three receptor species (Missale et al., 1998). 

The functions of Di and D2 receptors, and in part of D3, have been characterized in behavioral and biochemical studies, whereas the lack of highly selective compounds for the analysis of D4 and D5 receptors has hampered a full clarification of their functions. 

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Dopamine receptors are found primarily in brain, although they also exist in kidney [33]. Two subtypes of dopamine receptor were initially identified based primarily on differences in their drug specificities and signaling mechanisms. D receptors were found to stimulate adenylyl cyclase activity, while D2 receptors inhibited this enzyme (Fig. 12-6). Subsequently, multiple Dr and D2-like receptors were identified by molecular cloning (Table 12-3) [33], All dopamine receptor subtypes are... 

Some first-generation agents, such as haloperidol, are rather specific for one subtype of dopamine receptor, D2. This suggests that some degree of both efficacy and side effects are associated with dopamine antagonism at this receptor. However, the situation is complex, as usual. There are five classes of dopamine receptors known Di through D5. To complicate matters further, several of these classes have subclasses. In total, there are at least 15 dopamine receptors. Which of these is important for relief of the symptoms of schizophrenia Which is responsible for movement disorders The answers to these questions are incomplete. We do have a few hints. 

Dopamine has been implicated in a number of psychiatric conditions of which schizophrenia and the affective disorders are the most widely established. Five major subtypes of dopamine receptors have now been cloned. These are divided into two main groups, and D2 respectively. The receptors consist of Di and D5 types and are positively linked to the adenylate cyclase second messenger system, while the D2 group consists of the D2, D3 and D4 receptors which are negatively linked to the adenylate cyclase system. 

Five subtypes of dopamine receptors have been described they are the Dj-like and Dj-like receptor groups. All have seven transmembrane domains and are G protein-coupled. The Dj-receptor increases cyclic adenosine monophosphate (cAMP) formation by stimulation of dopamine-sensitive adenylyl cyclase it is located mainly in the putamen, nucleus accumbens, and olfactory tubercle. The other member of this family is the D5-receptor, which also increases cAMP but has a 10-fold greater affinity for dopamine and is found primarily in limbic regions. The therapeutic potency of antipsychotic drugs does not correlate with their affinity for binding to the Dj-receptor. 

Peripheral dopaminergic receptor agents are useful in the treatment of congestive heart failure (Figure 35.7). Two distinct subtypes of dopamine receptors have been identified. The dopamine2 (DA2)... 

Boyson SJ, McGonigie P, Molinoff PB (1986) Quantitative autoradiographic localization of the Di and D2 subtypes of dopamine receptors in rat brain. J Neurosci 6 3177-3188. 

As noted above, several different subtypes of dopamine receptors have been characterized by molecular methods, and both Dl-like and D2-like dopamine receptors are expressed by... 

Upon release from dopaminergic neurons, dopamine exerts its action by interacting with specific dopamine receptors. With molecular biological techniques five subtypes of dopamine receptors have been identified so far. These receptors have been characterised anatomically, and to a certain extent biochemically and pharmacologically. All currently identified dopamine receptor subtypes belong to the superfamily of G-protein-coupled receptors (GPCRs). 

Clozapine (Clozaril), a 5-HT2A/2c-receptor antagonist, represents a class of atypical antipsychotic drugs with reduced incidence of extrapyramidal side effects compared to the classical neuroleptics, and possibly a greater efficacy for reducing negative symptoms of schizophrenia. Clozapine also has a high affinity for subtypes of dopamine receptors. 

Peripheral dopaminergic receptor agents are useful in the treatment of congestive heart failure (CHF). Two distinct subtypes of dopamine receptors have been identified. The dopamine (DAi) receptors, which are located on vascular smooth muscles, cause vasodilation in the renal, mesentery, cerebral, and coronary vascular beds (see Figure 49). Thus, the pharmacologic response to activation of the DA2- and DAj-receptor receptors is hypotension, bradycardia, diuresis, and natriuresis. Fenoldopam is an orally active DA -receptor agonist. It is more potent than dopamine in causing... 

Dopamine is an important neurotransmitter in the CNS in ganglia of the limbic system and of the pituitary gland. It regulates the involuntary motoric, psychic processes and neuroendocrine functions. Dopamine also figures as a transmitter in synapses of the kidneys. More than 7 subtypes of dopamine receptors are recognized (Table 1). Whereas stimulation of D1-receptors inactivates adenylyl cyclase, D4.7 receptors activate this enzyme. D3-receptor activation leads to the closure of Ca2+ channels. 

Lidow etal. (1998) used in situ hybridization histochemistry to determine the laminar levels of the five distinct dopamine receptor mRNAs in the primate prefrontal cortex and to compare striatal and cortical levels. All five subtypes of dopamine receptor mRNA are present in both the monkey striatum and the cerebral cortex but in different proportions within each structure. 

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