5-Hydroxytryptamine 1D receptor (IPR000505)
Short name: 5HT1D_rcpt
Overlapping homologous superfamilies
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 5-HT1D receptor. It shares almost identical pharmacology with 5-HT1B receptor, but they differ in their level of expression: the level of 5-HT1D expression is very low compared with that of 5-HT1B receptors [PMID: 9559931, PMID: 9453271]. 5-HT1D receptors are found in neurons in the CNS and in vascular smooth muscles in the periphery, and affect locomotion and anxiety [PMID: 8736648, PMID: 8815958, PMID: 8750741, PMID: 15820416, PMID: 8736648, PMID: 23325368]. In the brain they are involved in vascular vasoconstriction and, as a result, 5-HT1D receptors are the therapeutic targets of the anti-migraine 'triptans' (e.g. sumitriptan and zolmitriptan), which are used to treat acute migraine attack [PMID: 10193663]. 5-HT1D receptors are also implicated in feeding behaviour, anxiety, depression. It has also been suggested that 5-HT1D receptors have a stimulatory effect on growth hormone secretion, possibly by inhibiting hypothalamic somatostatin release [PMID: 7775648, PMID: 10463324].
GO:0007186 G protein-coupled receptor signaling pathway
GO:0007268 chemical synaptic transmission
GO:0050795 regulation of behavior
GO:0040012 regulation of locomotion
GO:0006939 smooth muscle contraction
GO:0004993 G protein-coupled serotonin receptor activity
GO:0005887 integral component of plasma membrane