Oxytocin receptor

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



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

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

Oxytocin receptors are also present in the is_associated_with::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 is_associated_with::oxytocin article for more details.)

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

Mesolimbic dopamine pathways
The oxytocinergic circuit projecting from the is_associated_with::paraventricular hypothalamic nucleus (PVN) innervates the is_associated_with::ventral tegmental area (VTA) dopaminergic neurons that project to the is_associated_with::nucleus accumbens, i.e., the is_associated_with::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 is_associated_with::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 is_associated_with::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 is_associated_with::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 is_associated_with::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 is_associated_with::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 is_associated_with::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
 * is_associated_with::Carbetocin
 * is_associated_with::Demoxytocin
 * is_associated_with::Merotocin
 * is_associated_with::Oxytocin


 * Non-peptide
 * is_associated_with::TC OT 39 – non-selective over vasopressin receptors
 * is_associated_with::WAY-267,464 – is_associated_with::anxiolytic in mice; possibly non-selective over vasopressin receptors

Antagonists

 * Peptide
 * is_associated_with::Atosiban
 * is_associated_with::Barusiban


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