5-HT receptor

Source: Wikipedia, the free encyclopedia.
(Redirected from
Serotonin receptor
)
ribbon representation

5-HT receptors, 5-hydroxytryptamine receptors, or serotonin receptors, are a group of

neurotransmission. The serotonin (i.e., 5-hydroxytryptamine, hence "5-HT") receptors are activated by the neurotransmitter serotonin, which acts as their natural ligand
.

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

second messenger cascade to produce an excitatory or inhibitory response. The exception to this is the 5-HT3 receptor which is a ligand-gated ion channel
. In 2014, a novel 5-HT receptor was isolated from the small white butterfly, Pieris rapae, and named pr5-HT8. It does not occur in mammals and shares relatively low similarity to the known 5-HT receptor classes.[7]

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 clonedPDB 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 –
  • 7e2x
  • 7e2y
  • 7e2z

Yes Yes No No No No

Selective (for 5-HT1A over other 5-HT receptors)

Nonselective

5-HT1B 1992 –
  • 6g79
Yes Yes No No No No
  • triptans
    )
5-HT1D 1991 –
  • 7e32

Yes Yes No No No No
  • triptans
    )
5-HT1E
1992 –
  • 7e33

Yes Yes No No No No
  • None known
5-HT1F
1993 –
  • 7exd

No Yes No No No No
  • Migraine
  • None known
5-HT1P Not cloned No No Yes No No No
  • None known
5-HT2A 1988 Yes Yes Yes Yes Yes Yes
  • Addiction (potentially modulating)[54]
  • Anxiety[55]
  • Appetite
  • Cognition
  • Imagination
  • Learning
  • Memory
  • Mood
  • Perception
  • Sexual Behavior[56]
  • Sleep[57]
  • Thermoregulation[58]
  • Vasoconstriction[59]
5-HT2B 1992 Yes Yes Yes Yes Yes Yes
  • Migraines
    (antagonists)
5-HT2C 1988 Yes Yes Yes Yes Yes Yes
5-HT3 1993 No Yes Yes No Yes No
  • Addiction
  • Anxiety
  • Emesis
  • GI Motility[77]
  • Learning[78]
  • Memory[78]
  • Nausea
5-HT4 1995 No Yes Yes No Yes No
5-HT5A 1994 No Yes No No No No
  • None thus far
5-HT5B 1993 No No No No No No

Functions in rodents,
pseudogene in humans

  • None thus far
5-HT6 1993 No Yes No No No No
  • EMD-386,088
  • EMDT
  • WAY-181,187
  • WAY-208,466
  • E-6837
  • N-(inden-5-yl)imidazothiazole-5-sulfonamide (43)[97]
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

norepinephrine receptors.[38] LSD (a psychedelic) is a 5-HT1A, 5-HT2A, 5-HT2C, 5-HT5A and 5-HT6 agonist.[38]

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

  1. ^
    PMID 7938165
    .
  2. ^ .
  3. .
  4. .
  5. .
  6. .
  7. .
  8. .
  9. . Similarly, little is known about which of serotonin's 14 known receptors must be activated to achieve an antidepressant response.
  10. .
  11. ^ .
  12. ^ Glennon RA, Dukat M, Westkaemper RB (2000-01-01). "Serotonin Receptor Subtypes and Ligands". American College of Neurophyscopharmacology. Archived from the original on 21 April 2008. Retrieved 2008-04-11.
  13. ^ "5-Hydroxytryptamine Receptors". IUPHAR Receptor Database. International Union of Basic and Clinical Pharmacology. Retrieved 2008-04-11.
  14. PMID 12523486
    .
  15. .
  16. .
  17. .
  18. ^ .
  19. .
  20. .
  21. ^ .
  22. ^ .
  23. .
  24. ^ .
  25. .
  26. .
  27. .
  28. .
  29. .
  30. ^ .
  31. .
  32. ^ .
  33. ^ .
  34. .
  35. .
  36. .
  37. .
  38. ^ a b c d e f g h i j k l m n o p q r s t u Pharmacology Corner > Serotonin (5-HT): receptors, agonists and antagonists By Flavio Guzmán, M.D. on 9/08/09
  39. ^ a b c d e "BRINTELLIX (vortioxetine) tablets for oral use. Full Prescribing Information, Section 12.2 (Pharmacodynamics)." Takeda Pharmaceuticals America Inc. and Lundbeck, 2013. Revised September 2013. [1] Archived 2019-09-18 at the Wayback Machine
  40. PMID 2933009
    .
  41. .
  42. .
  43. .
  44. .
  45. ^ .
  46. ^ .
  47. ^ .
  48. .
  49. .
  50. .
  51. .
  52. .
  53. .
  54. ^ .
  55. .
  56. ^ .
  57. ^ .
  58. ^ .
  59. .
  60. ^ a b c McCall RB, Franklin SR, Hyslop DK, Knauer CS, Chio CL, Haber CL, Fitzgerald LW (2001). PNU-22394, a 5-HT2C receptor agonist, reduced feeding in rodents and produces weight loss in humans (Online). Society for Neuroscience. Vol. 27. Presentation Number 309.2. San Diego, CA: Society for Neuroscience Abstracts. p. TT-45. Retrieved 18 July 2014.
  61. ^
    PMID 19029184
    .
  62. ^ .
  63. .
  64. .
  65. .
  66. .
  67. .
  68. .
  69. ^ .
  70. ^ .
  71. .
  72. .
  73. .
  74. .
  75. .
  76. . Page 187
  77. .
  78. ^ .
  79. ^ .
  80. .
  81. .
  82. .
  83. ^ .
  84. ^ .
  85. .
  86. .
  87. .
  88. .
  89. .
  90. ^ .
  91. ^ .
  92. .
  93. ^ .
  94. .
  95. ^ .
  96. .
  97. .
  98. ^ "Target Schizophrenia - Possible future developments". The Association of the British Pharmaceutical Industry. Archived from the original on 2008-06-12. Retrieved 2008-04-11.
  99. ^
    S2CID 10998014
    .
  100. ^ .
  101. .
  102. .
  103. ^ .
  104. .
  105. .
  106. ^ Davies MA, Sheffler DJ, Roth BL. Aripiprazole: A Novel Atypical Antipsychotic Drug With a Uniquely Robust Pharmacology. CNS Drug Reviews [Internet]. 2004 [cited 2013 Aug 4];10(4):317–36. Available from: http://onlinelibrary.wiley.com/doi/10.1111/j.1527-3458.2004.tb00030.x/pdf
  107. ^ "HTR2C 5-hydroxytryptamine receptor 2C [ Homo sapiens (human) ]". NCBI. 19 Mar 2017. Retrieved 26 Mar 2017.
  108. PMID 26636753
    .
  109. .

External links