Ultimately the effects of monoamines on CNS function and behavior depend upon their interactions with receptor molecules. The binding of monoamines to these plasma membrane proteins initiates a series of intracellular events that modulate neuronal excitability. Unlike the transporters, multiple receptor subtypes exist for each monoamine transmitter. The initial classification of many receptor subtypes was based on radioligand binding studies. Receptor binding sites were identified on the basis of the rank order of binding affinities for a number of agonist and antagonist compounds. More recently, the molecular cloning of monoamine receptors has confirmed that many of the sites initially defined by these binding studies did indeed correspond to distinct receptor proteins encoded by unique genes. Molecular cloning has also led to the identification of previously unknown receptors, and to the introduction of powerful tools to characterize receptor structure and function.
[...] The functional roles of the peripheral adrenergic receptors are better understood than are its central functions. Cardiac b1 receptors play a major role in the regulation of heart function, and b2 receptors regulate bronchial muscle contraction. b3 receptors are found in adipose tissue, where they stimulate fat catabolism. Although b1 and b2 receptors are widely distributed in the CNS, their contributions to catecholamine function are not well understood. Propranolol (Inderal) is a widely used nonspecific antagonist of both b1 and b2 receptors. [...]
[...] The D3 and D4 receptors are considered to be D2-like on the basis of similarities in their gene structures, sequence homologies, and pharmacology. These receptors are expressed in lower abundance than the D2 receptor and their regional distributions are distinct. Whereas D3 receptor expression is high in the nucleus accumbens, highest levels of D4 receptors are expressed in the frontal cortex, midbrain, amygdala, and medulla. Whereas little D3 receptor expression has been detected outside the nervous system, D4 receptors are more abundant in the heart than in the brain. [...]
[...] Antagonists of H3 receptors have been proposed to have appetite suppressant, arousing, and cognitive- enhancing properties. Cholinergic Receptors Two major classes of cholinergic receptors exist: G protein–coupled muscarinic receptors and nicotinic ligand-gated ion channels. Muscarinic receptors have been implicated in learning and memory, sleep regulation, pain perception, and the regulation of seizure susceptibility. The five known subtypes of muscarinic receptors are heterogeneous with regard to regional brain distribution and primary effector mechanisms. The muscarinic type 1 M3, and M5 receptors stimulate phosphatidylinositol turnover, and the M2 and M4 receptors inhibit adenylate cyclase. [...]
[...] In addition, HT1D and 5-HT1F receptors are expressed in cerebral vessels, and are stimulated by the antimigraine drug sumatriptan (Imitrex). The relative importance of these receptors in the therapeutic efficacy of this drug remains to be determined. At least three receptor subtypes mediate the effects previously attributed to a single 5HT2 receptor subtype. The classic 5-HT2 receptor has thus been renamed 5-HT2A to indicate that it is a member of a serotonin receptor subfamily. A second receptor initially termed 5-HT1C has been renamed HT2C to indicate that it belongs within this subfamily. [...]
[...] The effects of both D1 and D2 receptor activation were attenuated in these animals; moreover, these mice were resistant to the hyperlocomotor effects of cocaine, indicating that D1 receptors contribute significantly to the effects of cocaine on the CNS. The D5 receptor was molecularly cloned on the basis of its sequence homology with the D1 receptor. The two receptors have a higher degree of homology with each other than with the D2 and D4 subtypes. This structural similarity is reflected in the similar affinities of a wide variety of dopaminergic drugs for these two receptors. [...]
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