HTR1D Membrane Protein Introduction

Introduction of HTR1D

5-hydroxytryptamine receptor 1D, alternatively called serotonin receptor 1D, is encoded by HTR1D gene in human. It is one of the subtypes for serotonin receptor (5-HT receptor) that binds the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT), and belongs to the G protein-coupled receptor (GPCR) family. HTR1D is predominantly expressed in the basal ganglia, hippocampus, cortex, spinal cord, and vascular smooth muscle cells, but also in the dorsal raphe and locus coeruleus. The HTR1D has 63% overall structural homology with the HTR1B and a 77% amino acid sequence homology in the seven-transmembrane domains.

Basic Information of HTR1D
Protein Name 5-hydroxytryptamine receptor 1D
Gene Name HTR1D
Aliases HTRL, RDC4, HT1DA, 5-HT1D, HTR1DA
Organism Homo sapiens (Human)
UniProt ID P28221
Transmembrane Times 7
Length (aa) 377

Function of HTR1D Membrane Protein

It has been suggested that neurogenic inflammation and nociceptive activity within the trigeminovascular afferents may be HTR1D mediated due to the presence of HTR1D in human trigeminal ganglia. When binding with its ligand 5-hydroxytryptamine (serotonin), HTR1D induces a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and regulates the activity of downstream effectors, such as adenylate cyclase. HTR1D signaling could inhibit adenylate cyclase activity. HTR1D acts on the central nervous system and affects locomotion and anxiety, specifically by regulating the release of 5-hydroxytryptamine in the brain and thereby affects neural activity. HTR1D also play a role in regulating the release of other neurotransmitters. Other studies show that HTR1D may be involved in vasoconstriction. What’s more, it also acts as a receptor for ergot alkaloid derivatives, various anxiolytic and antidepressant drugs and other psychoactive substances.

Structure of HTR1D membrane protein. Fig.1 Structure of HTR1D membrane protein.

Application of HTR1D Membrane Protein in Literature

  1. Saracheva K. E., et al. Effects of the novel high-affinity 5-HT(1B/1D)-receptor ligand frovatriptan on the rat carotid artery. Folia Med (Plovdiv). 2017, 59(1):31-36. PubMed ID: 28384110

    This study was carried out to evaluate the effect of frovatriptan, a specific anti-migraine drug, on isolated rat carotid artery. The observed contractile effect of frovatriptan was probably associated with the main effect of the drug-activation of the serotoninergic 5HT1B/1D receptors causing vasoconstriction of the cerebral vessels and their anti-migraine effect.

  2. Zhao X., et al. Serotonin type-1D receptor stimulation of A-type K(+) channel decreases membrane excitability through the protein kinase A- and B-Raf-dependent p38 MAPK pathways in mouse trigeminal ganglion neurons. Cell Signal. 2016, 28(8):979-88. PubMed ID: 27156838

    The results of this article indicated that the activation of 5-HT1D receptors selectively enhanced IA via the Gβγ of the Go-protein, PKA, and the sequential B-Raf-dependent p38 MAPK signaling cascade. This 5-HT1D receptor effect may contribute to neuronal hyperexcitability in small TG neurons.

  3. Thaweerattanasinp T., et al. Firing characteristics of deep dorsal horn neurons after acute spinal transection during administration of agonists for 5-HT1B/1D and NMDA receptors. J Neurophysiol. 2016, 116(4):1644-1653. PubMed ID: 27486104

    This study suggested that zolmitriptan, the 5-HT1B/1D receptor agonist, may exert its antispastic effect on the burst neurons via activation of 5-HT1B/1D receptors, whereas activation of NMDA receptors may facilitate the burst neurons in contributing to muscle spasm mechanisms following SCI (spinal cord injury).

  4. Vidal-Cantú G. C., et al. Role of 5-HT5A and 5-HT1B/1D receptors in the antinociception produced by ergotamine and valerenic acid in the rat formalin test. Eur J Pharmacol. 2016, 781:109-16. PubMed ID: 27068146

    The findings suggested that ergotamine and valerenic acid produced antinociception via 5-HT5A and 5-HT1B/1D receptors located at both spinal and peripheral sites.

  5. Tomić M. A., et al. The efficacy of eslicarbazepine acetate in models of trigeminal, neuropathic, and visceral pain: the involvement of 5-HT1B/1D serotonergic and CB1/CB2 cannabinoid receptors. Anesth Analg. 2015, 121(6):1632-9. PubMed ID: 26465930

    The findings revealed that the antinociceptive effect of ESL was, at least in part, mediated by 5-HT1B/1D serotonin and CB1/CB2 cannabinoid receptors in the trigeminal pain model.

HTR1D Preparation Options

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