5-HT receptor

The serotonin receptors, also known as 5-hydroxytryptamine receptors or 5-HT receptors, are a group of G protein-coupled receptors (GPCRs) and ligand-gated ion channels (LGICs) found in the central and peripheral nervous systems.[1][2] They mediate both excitatory and inhibitory neurotransmission. The serotonin receptors are activated by the neurotransmitter serotonin, which acts as their natural ligand.

The serotonin receptors modulate the release of many neurotransmitters, including glutamate, GABA, dopamine, epinephrine / norepinephrine, and acetylcholine, as well as many hormones, including oxytocin, prolactin, vasopressin, cortisol, corticotropin, and substance P, among others. The serotonin receptors influence various biological and neurological processes such as aggression, anxiety, appetite, cognition, learning, memory, mood, nausea, sleep, and thermoregulation. The serotonin receptors are the target of a variety of pharmaceutical and illicit drugs, including many antidepressants, antipsychotics, anorectics, antiemetics, gastroprokinetic agents, antimigraine agents, hallucinogens, and entactogens.[3]

Contents

Classification

With the exception of the 5-HT3 receptor, a ligand-gated ion channel, all other serotonin receptors are G protein-coupled receptors that activate an intracellular second messenger cascade to produce an excitatory or inhibitory response.

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 Na+ and K+ cation channel. Depolarizing plasma membrane. Excitatory
5-HT4 Gs-protein coupled. Increasing cellular levels of cAMP. Excitatory
5-HT5 Gi/Go-protein coupled.[4] 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

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

Overview of Serotonin Receptors
Receptor Gene(s) Distribution Function Agonists Antagonists
5-HT1A
  • Blood Vessels
  • CNS
5-HT1B
  • Blood Vessels
  • CNS
5-HT1D
  • Blood Vessels
  • CNS
5-HT1e putative receptor
  • Blood Vessels
  • CNS
5-HT1F
  • CNS
  • Migraine
  • LY334370
  • COL-144
5-HT2A
  • Blood Vessels
  • CNS
  • GI Tract
  • Platelets
  • PNS
  • Smooth Muscle
  • Addiction (potentially modulating) [40]
  • Anxiety[41]
  • Appetite
  • Cognition
  • Imagination
  • Learning
  • Memory
  • Mood
  • Perception
  • Sexual Behavior[42]
  • Sleep[43]
  • Thermoregulation[44]
  • Vasoconstriction[45]
5-HT2B
  • Blood Vessels
  • CNS
  • GI Tract
  • Platelets
  • PNS
  • Smooth Muscle
5-HT2C
  • Blood Vessels
  • CNS
  • GI Tract
  • Platelets
  • PNS
  • Smooth Muscle
5-HT3
  • CNS
  • GI Tract
  • PNS
  • Addiction
  • Anxiety
  • Emesis
  • GI Motility
  • Learning[59]
  • Memory[59]
  • Nausea
5-HT4
  • CNS
  • GI Tract
  • PNS
5-HT5A
  • CNS
5-HT6
  • CNS
5-HT7
  • Blood Vessels
  • CNS
  • GI Tract

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. Note that there is also no 5-HT5B receptor, as it exists only in mice and rats and not in humans or monkeys.

Very nonselective agonists of 5-HT receptor subtypes include ergotamine (an antimigraine), which activates 5-HT1A, 5-HT1D, 5-HT1B, D2 and norepinephrine receptors.[31] LSD (a psychedelic) is a 5-HT1A, 5-HT2A, 5-HT2C, 5-HT5A, 5-HT5, 5-HT6 agonist.[31]

References

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External links

Cys-loop receptors
5-HT/serotonin
5-HT3 (A, B, C, D, E)
GABAA (α1, α2, α3, α4, α5, α6, β1, β2, β3, γ1, γ2, γ3, δ, ε, π, θ) · GABAA-ρ (ρ1, ρ2, ρ3)
α1 · α2 · α3 · α4 · β
monomers: α1 · α2 · α3 · α4 · α5 · α6 · α7 · α9 · α10 · β1 · β2 · β3 · β4 · δ · ε
pentamers: (α3)2(β4)3 · (α4)2(β2)3 · (α7)5 · (α1)2(β4)3 - Ganglion type · (α1)2β1δε - Muscle type
Zinc
Ionotropic glutamates
Ligand-gated only
AMPA (1, 2, 3, 4) · Kainate (1, 2, 3, 4, 5)
Voltage- and ligand-gated
NMDA (1, 2A, 2B, 2C, 2D, 3A, 3B, L1A, L1B)
‘Orphan’
GluD (δ1, δ2)
ATP-gated channels
P2X (1, 2, 3, 4, 5, 6, 7)
B trdu: iter (nrpl/grfl/cytl/horl), csrc (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd; path (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)