5-Hydroxytryptamine 1F receptor (IPR000450)

Short name: 5HT1F_rcpt

Overlapping homologous superfamilies


Family relationships


5-hydroxytryptamine (5-HT) or serotonin, is a neurotransmitter that it is primarily found in the gastrointestinal (GI) tract, platelets, and in the central nervous system (CNS). It is implicated in a vast array of physiological and pathophysiological pathways. Receptors for 5-HT mediate both excitatory and inhibitory neurotransmission, and modulate the release of many neurotransmitters including glutamate, GABA, dopamine, epinephrine/norepinephrine, and acetylcholine, as well as many hormones, including oxytocin, prolactin, vasopressin and cortisol. In the CNS, 5-HT receptors can influence various neurological processes, such as aggression, anxiety and appetite and, as a, result are the target of a variety of pharmaceutical drugs, including many antidepressants, antipsychotics and anorectics [PMID: 18476671].

The 5-HT receptors are grouped into a number of distinct subtypes, classified according to their antagonist susceptibilities and their affinities for 5-HT. With the exception of the 5-HT3 receptor, which is a ligand-gated ion channel [PMID: 11989819], all 5-HT receptors are members of the rhodopsin-like G protein-coupled receptor family [PMID: 18476671], and they activate an intracellular second messenger cascade to produce their responses.

The 5-HT1 receptors are a subfamily of 5-HT receptors that were originally classified according to their inhibition of adenylyl cyclase, degree of sequence similarity and their overlapping pharmacological specificities. The subfamily is comprised of five different receptors 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, 5-HT1F, and they can couple to Gi/Go and mediate inhibitory neurotransmission, although signalling via other transduction systems are known. One of the 5-HT1 receptors, the 5-HT1E receptor, is yet to achieve receptor status from the International Union of Basic and Clinical Pharmacology (IUPHAR), since a robust response mediated via the protein has not been reported in the literature.

This entry represents the 5-HT1F receptors, they are thought to be closely related 5-HT1E receptors. They have a limited distribution in peripheral tissues in human, and have been detected only in the uterus and mesentery [PMID: 8380639]. In the CNS, receptor mRNA is present in the cerebral cortex, hippocampus, raphe and spinal cord [PMID: 10374714, PMID: 8380639, PMID: 8384716]. Elucidation of the physiological role of 5-HT1F receptors requires development of selective ligands. At present, there are no selective antagonists or agonists. However, the 5-HT1D/5-HTD1B agonist and anti-migraine compound sumatriptan has reasonable affinity. Interestingly, 5-HT1F receptor expression has been detected in the trigeminal ganglia, stimulation of which leads to the plasma extravasation in the dura, a component of neurogenic inflammation thought to be a possible cause of migraine [PMID: 11072640].

GO terms

Biological Process

GO:0007186 G-protein coupled receptor signaling pathway

Molecular Function

GO:0004993 G-protein coupled serotonin receptor activity

Cellular Component

GO:0005887 integral component of plasma membrane

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.