5-HT receptor

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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 drugs, including many antidepressants, antipsychotics, anorectics, antiemetics, gastroprokinetic agents, antimigraine agents, hallucinogens, and entactogens.[3]

The serotonin receptors are known to regulate longevity [4] and behavioral aging [5] in the nematode, Caenorhabditis elegans.

Classification[edit]

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[edit]

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.[6] 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[edit]

Within these general classes of serotonin receptors, a number of specific types have been characterized:[7][8][9]

Overview of Serotonin Receptors[edit]

Receptor
(first cloned)
Gene(s) Distribution Function Agonists Antagonists Uses of drugs that act on this receptor
5-HT1A
(1987)
  • Blood Vessels
  • CNS

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

Nonselective

5-HT1B
(1992)
  • Blood Vessels
  • CNS
5-HT1D
(1991)
  • Blood Vessels
  • CNS
5-HT1E
(1992)
  • Blood Vessels
  • CNS
  • None known
5-HT1F
(1993)
  • CNS
  • Migraine
  • None known
5-HT2A
(1988)
  • Blood Vessels
  • CNS
  • GI Tract
  • Platelets
  • PNS
  • Smooth Muscle
  • Addiction (potentially modulating) [45]
  • Anxiety[46]
  • Appetite
  • Cognition
  • Imagination
  • Learning
  • Memory
  • Mood
  • Perception
  • Sexual Behavior[47]
  • Sleep[48]
  • Thermoregulation[49]
  • Vasoconstriction[50]
5-HT2B
(1992)
  • Blood Vessels
  • CNS
  • GI Tract
  • Platelets
  • PNS
  • Smooth Muscle
5-HT2C
(1988)
  • Blood Vessels
  • CNS
  • GI Tract
  • Platelets
  • PNS
  • Smooth Muscle
5-HT3
(1993)
  • CNS
  • GI Tract
  • PNS
  • Addiction
  • Anxiety
  • Emesis
  • GI Motility
  • Learning[67]
  • Memory[67]
  • Nausea
5-HT4
(1995)
  • CNS
  • GI Tract
  • PNS
5-HT5A
(1994)
  • CNS
  • None thus far
5-HT5B
(1993)

functions in rodents,
pseudogene in humans

  • None thus far
5-HT6
(1993)
  • CNS
5-HT7
(1993)
  • 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.

Very nonselective agonists of 5-HT receptor subtypes include ergotamine (an antimigraine), which activates 5-HT1A, 5-HT1D, 5-HT1B, D2 and norepinephrine receptors.[33] LSD (a psychedelic) is a 5-HT1A, 5-HT2A, 5-HT2C, 5-HT5A, 5-HT5, 5-HT6 agonist.[33]

References[edit]

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