Oxytocin receptor

Oxytocin receptor
Identifiers
Symbols	OXTR ; OT-R
External IDs	OMIM: 167055 MGI: 109147 HomoloGene: 20255 IUPHAR: 369 ChEMBL: 2049 GeneCards: OXTR Gene
Gene ontology Molecular function • oxytocin receptor activity • vasopressin receptor activity • peptide hormone binding • peptide binding Cellular component • cytosol • plasma membrane • integral component of plasma membrane • microvillus • cell-cell adherens junction • apical plasma membrane Biological process • suckling behavior • response to amphetamine • regulation of systemic arterial blood pressure by vasopressin • muscle contraction • cell surface receptor signaling pathway • G-protein coupled receptor signaling pathway • positive regulation of cytosolic calcium ion concentration • heart development • female pregnancy • lactation • memory • positive regulation of norepinephrine secretion • telencephalon development • sleep • positive regulation of synaptic transmission, GABAergic • response to estradiol • response to progesterone • cellular response to hormone stimulus • response to anoxia • response to cytokine • social behavior • response to cocaine • response to drug • maternal behavior • sperm ejaculation • eating behavior • response to peptide hormone • estrous cycle • positive regulation of blood pressure • positive regulation of vasoconstriction • digestive tract development • positive regulation of synapse assembly • positive regulation of synaptic transmission, glutamatergic • maternal process involved in parturition • positive regulation of penile erection • negative regulation of gastric acid secretion • ERK1 and ERK2 cascade • positive regulation of uterine smooth muscle contraction • response to peptide Sources: Amigo / QuickGO
RNA expression pattern
File:PBB GE OXTR 206825 at tn.png
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	5021	18430
Ensembl	ENSG00000180914	ENSMUSG00000049112
UniProt	P30559	P97926
RefSeq (mRNA)	NM_000916	NM_001081147
RefSeq (protein)	NP_000907	NP_001074616
Location (UCSC)	Chr 3: 8.75 – 8.77 Mb	Chr 6: 112.47 – 112.49 Mb
PubMed search	[1]	[2]

The oxytocin receptor, also known as OXTR, is a protein which functions as receptor for the hormone and neurotransmitter oxytocin. In humans, the oxytocin receptor is encoded by the OXTR gene which has been localized to human chromosome 3p25.

File:OTR evolutionary tree.gif

Evolutionary tree of the oxytocin, vasotocin, mesotocin and isotocin receptors and their ligands. From Koechbach et al.

Function and location

The OXTR protein belongs to the G-protein coupled receptor family, specifically G_q, and acts as a receptor for oxytocin. Its activity is mediated by G proteins that activate several different second messenger systems.

Oxytocin receptors are expressed by the myoepithelial cells of the mammary gland, and in both the myometrium and endometrium of the uterus at the end of pregnancy. The oxytocin-oxytocin receptor system plays an important role as an inducer of uterine contractions during parturition and of milk ejection.

Oxytocin receptors are also present in the central nervous system. These receptors modulate a variety of behaviors, including stress and anxiety, social memory and recognition, sexual and aggressive behaviors, bonding (affiliation) and maternal behavior. (See the oxytocin article for more details.)

In some mammals, oxytocin receptors are also found in the kidney and heart.

Mesolimbic dopamine pathways

The oxytocinergic circuit projecting from the paraventricular hypothalamic nucleus (PVN) innervates the ventral tegmental area (VTA) dopaminergic neurons that project to the nucleus accumbens, i.e., the mesolimbic pathway. Activation of the PVN→VTA projection by oxytocin affects sexual, social, and addictive behavior via this link to the mesolimbic pathway; specifically, oxytocin exerts a prosexual and prosocial effect in this region.

Polymorphism

The receptors for oxytocin (OXTR) have genetic differences with different effects on individual behavior. The polymorphism (rs53576) occurs on the third intron of OXTR in three types: GG, AG, AA. The GG allele is connected with oxytocin levels in people. A-allele carrier individuals are associated with more sensitivity to stress, fewer social skills, and more mental health issues than the GG-carriers.

In a study looking at empathy and stress, individuals with the allele GG scored higher than A-carrier individuals in a “Reading the Mind in the Eyes” test. GG carriers, with their naturally higher levels of oxytocin, were better able to distinguish between emotions. A-allele carriers responded with more stress to stressful situations than GG-allele carriers. A-allele carriers had lower scores on psychological resources, like optimism, mastery, and self-esteem, than GG individuals when measured with factor analysis for depressive symptomology and psychological resources, along with the Beck Depression Inventory. A-allele carriers had higher depressive symptomology and lower psychological resources than GG individuals. A-allele individuals scored lower in human sociality than GG people on a Tridimensional Personality Questionnaire. AA individuals had the lowest amygdala activation while processing emotionally salient information and those with GG had the highest activity when tested using BOLD during an fMRI.

A study looking at facial recognition in British and Finnish families with a single high-functioning autistic child found that a single change in the DNA had a major impact on face memory, with AA individuals having impaired SD scores.

The frequency of the A allele varies among ethnic groups, being significantly more common among East Asians than Europeans.

Ligands

Several selective ligands for the oxytocin receptor have recently been developed, but close similarity between the oxytocin and related vasopressin receptors make it difficult to achieve high selectivity with peptide derivatives. However the search for a druggable, non-peptide template has led to several potent, highly selective, orally bioavailable oxytocin antagonists.

Agonists

Peptide

• Carbetocin
• Demoxytocin
• Lipo-oxytocin-1
• Merotocin
• Oxytocin

Non-peptide

• TC OT 39 – non-selective over vasopressin receptors
• WAY-267,464 – anxiolytic in mice; possibly non-selective over vasopressin receptors

Antagonists

Peptide

• Atosiban
• Barusiban

Non-peptide

• Epelsiban
• L-368,899 (CAS# 148927-60-0)
• L-371,257 (CAS# 162042-44-6) – peripherally selective (i.e. poor blood brain barrier penetration, few central effects)
• L-372,662
• Retosiban (GSK-221,149)
• SSR-126,768
• WAY-162,720 – centrally active following peripheral administration

External links

• Oxytocin receptor at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.