Proposals for the classification and nomenclature of functional receptors for 5-hydroxytryptamine

The neurotransmitter serotonin (5HT) activates a variety of second messenger signaling systems and through them indirectly regulates the function of ion channels. Serotonin also activates ion channels directly, suggesting that it may also mediate rapid, excitatory responses. A complementary DNA clone containing the coding sequence of one of these rapidly responding channels, a 5HT3 subtype of the serotonin receptor, has been isolated by screening a neuroblastoma expression library for functional expression of serotonin-gated currents in Xenopus oocytes. The predicted protein product has many of the features shared by other members of the ligand-gated ion channel family. The pharmacological and electrophysiological characteristics of the cloned receptor are largely consistent with the properties of native 5HT3 receptors. Messenger RNA encoding this receptor is found in the brain, spinal cord, and heart. This receptor defines a new class of excitatory ligand-gated channels.

https://science.sciencemag.org/content/sci/254/5030/432.full.pdf

Primary structure and functional expression of the 5HT3 receptor, a serotonin-gated ion channel

Molecular biology of 5-HT receptors

Peripheral and central mechanisms of cutaneous hyperalgesia.

Neurons that release serotonin as a neurotransmitter project to most regions of the central and peripheral nervous system and mediate diverse neural functions. The physiological effects of serotonin are initiated by the activation of multiple, distinct receptor subtypes. Cloning in RNA expression vectors was combined with a sensitive electrophysiological assay in Xenopus oocytes in order to isolate a functional cDNA clone encoding the 5HTlc serotonin receptor. Injection of RNA transcribed in vitro from this clone into Xenopus oocytes elicits serotonin sensitivity. Mouse fibroblasts transformed with this clone bind serotonin agonists and antagonists and exhibit an increase in intracellular Ca2+ concentrations in response to serotonin. The sequence of the 5HTlc receptor reveals that it belongs to the family of G protein-coupled receptors, which are thought to traverse the cytoplasmic membrane seven times. Moreover, in situ hybridization and RNA blot analysis indicate that the 5HTlc receptor is expressed in neurons in many regions of the central nervous system and suggest that this subclass of receptor may mediate many of the central actions of serotonin.

https://science.sciencemag.org/content/sci/241/4865/558.full.pdf

Molecular characterization of a functional cDNA encoding the serotonin 1c receptor.

We describe a new class of drugs that selectively block serotonin M-receptors on peripheral neurones. Because of their high affinity, some of these drugs are the most potent of any pharmacological class yet reported. They have allowed the identification of three M-receptor subtypes, one of which is responsible for mediating the painful effects of serotonin in humans.

Identification of serotonin M-receptor subtypes and their specific blockade by a new class of drugs

Subtypes of neuronal 5 hydroxy tryptamine receptors as identified by competitive antagonists

Inhibition of noradrenaline (NA)-induced cardiac arrhythmias in the rat by ICS 205–930

Receptors for 5-hydroxytryptamine (5-HT) are widely distributed over the mammalian peripheral nervous system (Wallis, 1981; Fozard, 1984). Those located on afferent neurones generally mediate excitatory actions of 5-HT, with neuronal inhibition being only rarely encountered (Paintal, 1973; Wallis, 1981; Roberts, 1984; Higashi and Nishi, 1982). Until recently it was unclear which receptor subtype mediates the stimulant action of 5-HT on primary afferent neurones, because such responses are refractory to blockade by the older, classical 5-HT receptor antagonists such as methysergide or cyproheptadine (Fozard, 1984). However, the recent discovery of new agonist and antagonist drugs with a high degree of selectivity for the different 5-HT receptor subtypes (Bradley et al., 1986; Richardson and Engel, 1986; Saxena et al., 1986) has stimulated renewed interest in this topic.

P. Donatsch

Papers

Identification of serotonin M-receptor subtypes and their specific blockade by a new class of drugs

Subtypes of neuronal 5 hydroxy tryptamine receptors as identified by competitive antagonists

Inhibition of noradrenaline (NA)-induced cardiac arrhythmias in the rat by ICS 205–930

5-HT Receptors on Afferent Neurones