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    • br There are three types of HT receptors

    2024-05-16


    There are three types of 5-HT2 receptors. 5-HT2A, 5-HT2B and 5-HT2C receptors Exhibit 46–50% overall sequence identity and couple preferentially to Gq/11 to increase inositol phosphates and cytosolic [Ca2+] and in agreement with their long known role in muscle contraction and stimulation in the brain. 5-HT2 receptors may also couple to G12/13 which are known to mediate long term structural changes in cells. The 5-HT2A receptor refers to the classical D receptor initially described by Gaddum and Picarelli [89], and later defined as the 5-HT2 receptor by Peroutka and Snyder [90]. 5-HT2B receptors were characterized almost 30 years ago to mediate the contractile action of 5-HT in the rat fundus, (but the 5-HT2B receptor had escaped any meaningful classification, our own group had tried to establish that the fundus receptor was of the 5-HT2C type, but the idea was abandoned). When cloned they were initially named 5-HT2F (for fundus). In human pulmonary artery endothelial cells, 5-HT2B receptor stimulation causes intracellular Ca2+ release and potent contraction. The third 5-HT2 receptor subtype corresponds to the previously known 5-HT1C receptor, it was initially identified in the choroid plexus, where both [3H]5-HT and [3H]mesulergine showed high affinity binding, with superimposable profile (thus the initial 5-HT1 appelation).
    5-HT3 receptors equate with the M receptor of Gaddum and Picarelli [89]; they belong to the ligand-gated ion channel receptor superfamily, similarly to the nicotinic acetylcholine, glycine or GABA-A receptors and share electrophysiological and structural patterns with the Cys-loop transmitter-gated superfamily of ligand-gated ion Flubendazole [140]. There are antagonist ligands that share affinity at 5-HT3 and nicotine receptors, such as tropisetron (ICS-205930). 5-HT3 receptors are located on central and peripheral neurons, where they trigger rapid depolarization due to the opening of non-selective cation channels (Na+, Ca++ influx, K+ efflux) ([5], [6]; Martin et al., 2000). The response desensitises and resensitises rapidly. The native 5-HT3 receptor, as revealed by electron microscopy in neuroblastoma-glioma cells, is a pentamer with the 5 subunits surrounding a central channel [141]. To date, two genes have been recognized to encode 5-HT3 receptors: the 5-HT3A receptor subunit [142] has 487 amino acids and displays a high level of identity with other members of the Cys-Cys loop ligand-gated ion channel superfamily (e.g. nicotinic, GABAA, and glycine receptors). A second subunit was isolated from various species, 5-HT3B, which codes for 441 amino acids in humans [143]: 5-HT3B as a homopentamer is not active. 5-HT3C,D,E have been reported as sequences, but until recently no report confirmed any 5-HT3 direct role of these subunits, although a chaperone function may well exit ([144], see below).
    5-HT receptors that preferentially couple to Gs 5-HT4, 5-HT6 and 5-HT7 receptors all couple preferentially to Gs and promote cAMP formation, by activation of various adenylate cyclases. In turn, cAMP as an intracellular messenger interacts with various targets, the phosphorylating enzyme protein kinase A (PKA), but also cyclic nucleotide-gated ion channels, leading to the modulation of calcium ion flux and membrane excitability, other cellular processes. PKA phosphorylates cAMP-responsive transcription factors, such as the cAMP response element binding protein (CREB), which leads to changes in gene expression, and thus may promote long term changes in cellular responses. Further, cAMP seems to interact with a family of cAMP sensors called Epac (exchange proteins directly activated by cAMP). Epacs mediate PKA-independent signal transduction, e.g. activation of Rap and Ras GTPases, and possibly other important cellular proteins. 5-HT4, 5-HT6 and 5-HT7 receptors are considered as distinct receptor classes because of their limited (<35%) overall sequence identities, which are much lower as those featured by either 5-HT1 or 5-HT2 receptors. This subdivision is arbitrary and may be subject to future modification. On the other hand, 5-ht5 receptors form a class a part, as neither G-protein-coupling nor function are clearly defined.