5-HT Receptor Wiki resources & 5-HT Receptor information at HealthHaven.com

5-HT receptor:

In the field of neurochemistry, 5-HT receptors are receptors for the neurotransmitter and peripheral signal mediator serotonin, also known as 5-hydroxytryptamine or 5-HT.^[1]^[2] 5-HT receptors are located on the cell membrane of nerve cells and other cell types including smooth muscle in animals, and mediate the effects of serotonin as the endogenous ligand and of a broad range of pharmaceutical and hallucinogenic drugs. 5-HT receptors affect the release and activity of other neurotransmitters such as glutamate, dopamine and GABA. 5-HT_2A receptors increase the activity of glutamate in many areas of the brain, while some other serotonin receptors have the effect of suppressing glutamate. Increased stimulation of 5-HT_2A receptors seem to oppose the therapeutic actions of increased stimulation of other serotonin receptors in anti-depressant and anxiolytic treatments.^[3]

Serotonin

1 Classification
- 1.1 Families
- 1.2 Specific proteins/genes
2 Therapeutic modulation
3 References
4 External links

[edit] Classification

With the exception of the 5-HT₃ receptor, a ligand gated ion channel, all other 5-HT receptors are G protein coupled seven transmembrane (or heptahelical) receptors that activate an intracellular second messenger cascade.

[edit] Families

Family	Type	Mechanism
5-HT₁	G_i/G_o coupled	decreasing cellular levels of cAMP
5-HT₂	G_q/G₁₁ coupled	increasing cellular levels of inositol trisphosphate (IP₃) and diacylglycerol (DAG)
5-HT₃	ligand-gated Na⁺ and K⁺ cation channel	depolarizing plasma membrane
5-HT₄	G_s coupled	increasing cellular levels of cAMP
5-HT_5A	G protein coupled; the primary coupling appears to be through Gi/o	inhibiting adenylate cyclase activity.^[4]
5-HT₆	G_s coupled	increasing cellular levels of cAMP
5-HT₇	G_s coupled	increasing cellular levels of cAMP

[edit] Specific proteins/genes

Within these general classes of 5-HT receptors, a number of specific types have been characterized:^[5]^[6]^[7]

Receptor	Gene	Actions	Agonists	Antagonists
Summary of characterized 5-HT receptors with selected high affinity agonist and antagonist ligands, both ones of major importance and others
5-HT_1A	HTR1A	CNS: neuronal inhibition, behavioural effects (sleep, feeding, thermoregulation, aggression, anxiety)	buspirone LSD psilocin MDMA (speculated)^[8] 5-CT 8-OH-DPAT flesinoxan U-92016A^[9] vilazodone	ergotamine pindolol yohimbine methiothepin robalzotan spiperone WAY-100135 WAY-100635^[10]
5-HT_1B	HTR1B	CNS: presynaptic inhibition, behavioural effects vascular: pulmonary vasoconstriction	ergotamine sumatriptan	risperidone yohimbine metergoline methiothepin
5-HT_1D	HTR1D	CNS: locomotion, anxiety; vascular: cerebral vasoconstriction	sumatriptan 5-(Nonyloxy)tryptamine^[11]	ergotamine yohimbine metergoline methiothepin
5-HT_1E	HTR1E		BRL-54443 LSD (very low)
5-HT_1F	HTR1F		BRL-54443 LY-334,370 LY-344,864
5-HT_2A	HTR2A	CNS: neuronal excitation, behavioural effects, learning, anxiety smooth muscle: contraction, vasoconstriction / vasodilatation platelets: aggregation	mescaline psilocin α-methyl-5-HT 5-MeO-AMT DMT LSD TCB-2	ketanserin mirtazapine nefazodone pizotifen trazodone atypical antipsychotics cyproheptadine
5-HT_2B	HTR2B	stomach: contraction	LSD Fenfluramine α-methyl-5-HT DOI	yohimbine
5-HT_2C	HTR2C	CNS: anxiety, choroid plexus: cerebrospinal fluid (CSF) secretion	Lorcaserin LSD psilocin α-methyl-5-HT DOI	fluoxetine methysergide^[12] agomelatine mesulergine SB-242,084
5-HT₃	HTR3A, HTR3B	CNS, PNS: neuronal excitation, anxiety, emesis	2-methyl-5-HT	alosetron memantine metoclopramide (high doses) mirtazapine ondansetron renzapride
5-HT₄	HTR4	GIT: gastrointestinal motility CNS: neuronal excitation, learning, memory	cisapride metoclopramide tegaserod 5-MT renzapride RS 67333	GR-113,808 Piboserod
5-HT_5A	HTR5A	CNS (cortex, hippocampus, cerebellum): unknown	LSD^[4] 5-CT
5-HT₆	HTR6	CNS: regulates glutamate and acetylcholine release	LSD EMDT EMD-386,088	SB-271,046^[13] SB-258,585 SB-357,134 SB-399,885
5-HT₇	HTR7	CNS, GIT, blood vessels: unknown	5-CT LSD AS-19	risperidone methiothepin

Note that there is no 5-HT_1C 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-HT_2C receptor.

[edit] Therapeutic modulation

Various drugs are used to modulate the 5-HT system including some antidepressants, anxiolytics, antiemetics, antipsychotics and anti-migraine agents.^[14]

[edit] References

^ Hoyer D, Clarke DE, Fozard JR, Hartig PR, Martin GR, Mylecharane EJ, Saxena PR, Humphrey PP (1994). "International Union of Pharmacology classification of receptors for 5-hydroxytryptamine (Serotonin)". Pharmacol. Rev. 46 (2): 157–203. PMID 7938165, http://pharmrev.aspetjournals.org/cgi/content/abstract/46/2/157.
^ Frazer A, Hensler JG (1999). "Chapter 13: Serotonin Receptors", in Siegel GJ, Agranoff BW, Albers RW, Fisher SK, Uhler MD, editors: Basic Neurochemistry: Molecular, Cellular, and Medical Aspects. Philadelphia: Lippincott-Raven, pages 263-292. ISBN 0-397-51820-X. Retrieved on 2008-04-11.
^ Marek GJ, Carpenter LL, McDougle CJ, Price LH (2003). "Synergistic action of 5-HT2A antagonists and selective serotonin reuptake inhibitors in neuropsychiatric disorders". Neuropsychopharmacology 28 (2): 402–12. doi:10.1038/sj.npp.1300057. PMID 12589395.
^ ^a ^b Nelson DL (2004). "5-HT₅ receptors". Current drug targets. CNS and neurological disorders 3 (1): 53–8. PMID 14965244, http://www.ingentaconnect.com/content/ben/cdtcnsnd/2004/00000003/00000001/art00006.
^ Glennon RA, Dukat M, Westkaemper RB (2000-01-01). "Serotonin Receptor Subtypes and Ligands". American College of Neurophyscopharmacology. Retrieved on 2008-04-11.
^ "5-Hydroxytryptamine Receptors". IUPHAR Receptor Database. International Union of Basic and Clinical Pharmacology. Retrieved on 2008-04-11.
^ Wesołowska A (2002). "In the search for selective ligands of 5-HT₅, 5-HT₆ and 5-HT₇ serotonin receptors" (PDF). Polish Journal of Pharmacology 54 (4): 327–41. PMID 12523486, http://www.if-pan.krakow.pl/pjp/pdf/2002/4_327.pdf.
^ Thompson MR, Callaghan PD, Hunt GE, Cornish JL, McGregor IS.. A role for oxytocin and 5-HT(1A) receptors in the prosocial effects of 3,4 methylenedioxymethamphetamine ("ecstasy")., http://www.mdma.net/oxytocin-release/index.html.
^ McCall RB, Romero AG, Bienkowski MJ, Harris DW, McGuire JC, Piercey MF, Shuck ME, Smith MW, Svensson KA, Schreur PJ, et al. (1994). "Characterization of U-92016A as a selective, orally active, high intrinsic activity 5-hydroxytryptamine_1A agonist.". J. Pharmacol. Exp. Ther. 271 (2): 875-883. PMID 7965808, http://jpet.aspetjournals.org/cgi/content/abstract/271/2/875.
^ Fornal CA, Metzler CW, Gallegos RA, Veasey SC, McCreary AC, Jacobs BL (1996). "WAY-100635, a potent and selective 5-hydroxytryptamine_1A antagonist, increases serotonergic neuronal activity in behaving cats: comparison with (S)-WAY-100135". J. Pharmacol. Exp. Ther. 278 (2): 752–62. PMID 8768728, http://jpet.aspetjournals.org/cgi/content/abstract/278/2/752.
^ Glennon RA, Hong SS, Dukat M, Teitler M, Davis K (1994). "5-(Nonyloxy)tryptamine: a novel high-affinity 5-HT_1D beta serotonin receptor agonist". J. Med. Chem. 37 (18): 2828–30. doi:10.1021/jm00044a001. PMID 8071931.
^ Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. ISBN 0-443-07145-4. Page 187
^ "Target Schizophrenia - Possible future developments". The Association of the British Pharmaceutical Industry. Retrieved on 2008-04-11.
^ Nichols DE, Nichols CD (May 2008). "Serotonin receptors". Chem. Rev. 108 (5): 1614–41. doi:10.1021/cr078224o. PMID 18476671.

[edit] External links

MeSH Serotonin+Receptors
"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 on 2008-04-11.

v • d • e

Transmembrane receptor: G protein-coupled receptors

Class A: Rhodopsin like

Adrenergic	α1 (A, B, D) • α2 (A, B, C) • β1 • β2 • β3

Eicosanoid	CysLT (1, 2) • LTB4 (1, 2) • FPRL1 • OXE • Prostaglandin (DP, EP (1, 2, 3, 4), PGF) • Prostacyclin • Thromboxane

Neuropeptide	B/W (1, 2) • FF (1, 2) • S • Y (1, 2, 4, 5) • Neuromedin (B, U (1, 2)) • Neurotensin (1, 2)

Orphan	GPR (1, 3, 4, 6, 12, 15, 17, 18, 19, 20, 21, 22, 23, 25, 26, 27, 31, 32, 33, 34, 35, 37, 39, 42, 44, 45, 50, 52, 55, 61, 62, 63, 65, 68, 75, 77, 78, 82, 83, 84, 85, 87, 88, 92, 101, 103, 119, 120, 132, 135, 139, 141, 142, 146, 148, 149, 150, 151, 152, 153, 160, 161, 162, 171, 172A, 173, 174, 176, 177, 182)

Purinergics	Adenosine (A1, A2a, A2b, A3) • P2Y (1, 2, 4, 5, 6, 8, 9, 10, 11, 12, 13, 14)

Serotonin	(all but 5-HT3) 5-HT1 (A, B, D, E, F) • 5-HT2 (A, B, C) • 5-HT (4, 5A, 6, 7)

Other	Acetylcholine (M1, M2, M3, M4, M5) • Adrenomedullin • Anaphylatoxin (C3a, C5a) • Angiotensin (1, 2) • Apelin • Bile acid • Bombesin (BRS3, GRPR, NMBR) • Bradykinin (B1, B2) • Cannabinoid (CB1, CB2) • Chemokine • Cholecystokinin (A, B) • Dopamine (D1, D2, D3, D4, D5) • EBI2 • Endothelin (A, B) • Estrogen • Formyl peptide (1, L1, L2) • Free fatty acid (1, 2, 3, 4) • FSH • Galanin (1, 2, 3) • Gonadotropin-releasing hormone (1, 2) • Ghrelin • Histamine (H1, H2, H3, H4) • Kisspeptin • Luteinizing hormone/choriogonadotropin • Lysophospholipid (1, 2, 3, 4, 5, 6, 7, 8) • MAS (1, 1L, D, E, F, G, X1, X2, X3, X4) • Melanocortin (1, 2, 3, 4, 5) • MCHR (1, 2) • Melatonin (1A, 1B) • Motilin • Opioid (Delta, Kappa, Mu, Nociceptin, but not Sigma) • Olfactory • Opsin (3, 4, 5, 1LW, 1MW, 1SW, RGR, RRH) • Orexin (1, 2) • Oxytocin • Oxoglutarate • PAF • Prokineticin (1, 2) • Prolactin-releasing peptide • Protease-activated (1, 2, 3, 4) • Relaxin (1, 2, 3, 4) • Somatostatin (1, 2, 3, 4, 5) • SREB • Succinate • TAAR (1, 2, 3, 5, 6, 8, 9) • Tachykinin (1, 2, 3) • Thyrotropin • Thyrotropin-releasing hormone • Urotensin-II • Vasopressin (1A, 1B, 2)

Class B: Secretin like

Orphan	GPR (56, 64, 97, 98, 110, 111, 112, 113, 114, 115, 116, 123, 124, 125, 126, 128, 133, 143, 144, 157)

Other	Brain-specific angiogenesis inhibitor (1, 2, 3) • Cadherin (1, 2, 3) • Calcitonin • CALCRL • CD97 • Corticotropin-releasing hormone (1, 2) • EMR (1, 2, 3) • Glucagon (GR, GIPR, GLP1R, GLP2R) • Growth hormone releasing hormone • PACAPR1 • GPR • Latrophilin (1, 2, 3, ELTD1) • Parathyroid hormone (1, 2) • Secretin • Vasoactive intestinal peptide (1, 2)

Class C: Metabotropic
glutamate / pheromone

Taste	TAS1R (1, 2, 3) • TAS2R (1, 3, 4, 5, 8, 9, 10, 12, 13, 14, 16, 38, 39, 40, 41, 43, 44, 45, 46, 47, 48, 49, 50)

Other	Calcium-sensing receptor • GABA B (1, 2) • Glutamate receptor (Metabotropic glutamate (1, 2, 3, 4, 5, 6, 7, 8)) • GPRC6A • GPR (156, 158, 179) • RAIG (1, 2, 3, 4)

Frizzled / Smoothened

Frizzled (1, 2, 3, 4, 5, 6, 7, 8, 9, 10) • Smoothened

v • d • e

Ion channel, receptor: ligand-gated ion channels

Cys-loop receptors

5-HT/serotonin	5-HT₃ (A, B, C, D, E)

GABA	GABA A (α₁, α₂, α₃, α₄, α₅, α₆, β₁, β₂, β₃, γ₁, γ₂, γ₃, δ, ε, π, θ) • GABA C (ρ₁, ρ₂, ρ₃)

Glycine	α₁ • α₂ • α₃ • α₄ • β

Nicotinic acetylcholine	monomers: α1 • α2 • α3 • α4 • α5 • α6 • α7 • α9 • α10 • β1 • β2 • β3 • β4 • δ • ε pentamers: (α4)₂(β2)₃ • (α7)₅ • (α1)₂(β4)₃ - Ganglion type • (α1)₂β1δε - Muscle type