5-HT receptor
5-HT receptors, 5-hydroxytryptamine receptors, or serotonin receptors, are a group of
The serotonin receptors modulate the release of many neurotransmitters, including
Serotonin receptors are found in almost all animals and are even known to regulate longevity and behavioral aging in the primitive nematode, Caenorhabditis elegans.[5][6]
Classification
5-hydroxytryptamine receptors or 5-HT receptors, or serotonin receptors are found in the central and peripheral nervous systems.[1][2] They can be divided into 7 families of
Families
Family | Type | Mechanism | Potential |
5-HT1 |
Gi/Go-protein coupled. | Decreasing cellular levels of cAMP. | Inhibitory |
5-HT2 |
Gq/G11 -protein coupled. |
Increasing cellular levels of IP3 and DAG. | Excitatory |
5-HT3 |
Ligand-gated cation channel . |
plasma membrane . |
Excitatory |
5-HT4 |
Gs -protein coupled. |
Increasing cellular levels of cAMP. | Excitatory |
5-HT5 |
Gi/Go-protein coupled.[8] | Decreasing cellular levels of cAMP. | Inhibitory |
5-HT6 |
Gs -protein coupled. |
Increasing cellular levels of cAMP. | Excitatory |
5-HT7 |
Gs -protein coupled. |
Increasing cellular levels of cAMP. | Excitatory |
Subtypes
The 7 general serotonin receptor classes include a total of 14 known serotonin receptors.[9] The 15th receptor 5-HT1P has been distinguished on the basis of functional and radioligand binding studies, its existence has never been definitely affirmed or refuted.[10][11] The specific types have been characterized as follows:[12][13][14]
Information on serotonin receptors (human isoforms if nothing else is stated) | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Receptor | First cloned – PDB entries | Gene(s) | Distribution | Function | Agonists | Antagonists | Uses of drugs that act on this receptor | |||||
Blood vessels | CNS | GI Tract | Platelets | PNS | Smooth Muscle
| |||||||
5-HT1A | 1987 –
|
Yes | Yes | No | No | No | No |
|
Selective (for 5-HT1A over other 5-HT receptors)
Nonselective
|
|
| |
5-HT1B | 1992 –
|
Yes | Yes | No | No | No | No |
|
|
| ||
5-HT1D | 1991 –
|
Yes | Yes | No | No | No | No |
|
|
|
| |
5-HT1E
|
1992 –
|
Yes | Yes | No | No | No | No |
| ||||
5-HT1F
|
1993 –
|
No | Yes | No | No | No | No |
|
|
| ||
5-HT1P | Not cloned | No | No | Yes | No | No | No |
| ||||
5-HT2A | 1988 | Yes | Yes | Yes | Yes | Yes | Yes |
| ||||
5-HT2B | 1992 | Yes | Yes | Yes | Yes | Yes | Yes |
|
| |||
5-HT2C | 1988 | Yes | Yes | Yes | Yes | Yes | Yes |
|
| |||
5-HT3 | 1993 | No | Yes | Yes | No | Yes | No |
|
| |||
5-HT4 | 1995 | No | Yes | Yes | No | Yes | No |
| ||||
5-HT5A | 1994 | No | Yes | No | No | No | No |
|
|
|
| |
5-HT5B | 1993 | No | No | No | No | No | No |
Functions in rodents, |
| |||
5-HT6 | 1993 | No | Yes | No | No | No | No |
|
| |||
5-HT7 | 1993 | Yes | Yes | Yes | No | No | No |
|
|
Note that there is no 5-HT1C receptor since, after the receptor was cloned and further characterized, it was found to have more in common with the 5-HT2 family of receptors and was redesignated as the 5-HT2C receptor.[107]
Very nonselective agonists of 5-HT receptor subtypes include
Expression patterns
The genes coding for serotonin receptors are expressed across the mammalian brain. Genes coding for different receptors types follow different developmental curves. Specifically, there is a developmental increase of HTR5A expression in several subregions of the human cortex, paralleled by a decreased expression of HTR1A from the embryonic period to the post-natal one. [108]
5-HT1-like
A number of receptors were classed as "5-HT1-like" - by 1998 it was being argued that, since these receptors were "a heterogeneous population of 5-HT1B, 5-HT1D and 5-HT7" receptors the classification was redundant.[109]
References
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External links
- Serotonin+Receptors at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- "5-Hydroxytryptamine Receptors". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
- Rubenstein LA, Lanzara RG (2005-02-16). "Activation of G protein-coupled receptors entails cysteine modulation of agonist binding". Cogprints. Retrieved 2008-04-11.
- Paterson LM, Kornum BR, Nutt DJ, Pike VW, Knudsen GM (January 2013). "5-HT radioligands for human brain imaging with PET and SPECT". Medicinal Research Reviews. 33 (1): 54–111. PMID 21674551.