TAAR1

TAAR1
المعهدات
الأسماء المستعارة	TAAR1, TA1, TAR1, TRAR1, trace amine associated receptor 1, Trace amine receptor
معهدات خارجية	الوراثة المندلية البشرية عبر الإنترنت 609333 MGI: MGI:2148258 HomoloGene: 24938 GeneCards: 134864
فهم الوجود الجيني
الوظيفة الجزيئية	• G-protein coupled amine receptor activity; • signal transducer activity; • G-protein coupled receptor activity; • trace-amine receptor activity;
المكونات الخلوية	• غشاء خلوي; • غشاء; • مكون تكاملي للغشاء;
العمليات الحيوية	• توصيل الإشارة; • G-protein coupled receptor signaling pathway;
	المصادر:Amigo / QuickGO
نمط التعبير عن الحمض النووي الريبوزي
	المزيد من بيانات التعبير المرجعية
أورثولوج
	Q96RJ0
	Q923Y8
	NM_138327
	NM_053205
	NP_612200
	NP_444435
	ويكي بيانات
اعرض/عدّل إنسان	اعرض/عدّل فأر

المستقبل المرتبط بالأمين النزر1 (تار1 : TAAR1) هوبروتين، مستقبل مرتبط بأمين نزر (TAAR) يشفر لدى البشر بواسطة الجين TAAR1. تار1 هومستقبل مقترن بالبروتين ج داخل خلوي منشَّط بالأمين ومقترن بـ Gs وGq، يعبر عنه بشكل أساسي في الكثير من الأعضاء والخلايا (مثل: المعدة، الأمعاء الدقيقة، الإثنا عشر وخلايا الدم البيضاء)، الخلايا النجمية وفي الوسط داخل الخلوي بمحاذاة الغشاء البلازمي قبل المشبكي (نهاية المحوار) للعصبونات أحادية الأمين في الجهاز العصبي المركزي. اكتُشف تار1 سنة 2001 بواسطة مجموعتين مستقلتين من الباحثين بوروفسكي وزملاؤه وبانزووزملاؤه. تار1 أحد ستة مستقبلات مرتبطة بأمين نزر بشرية وظيفية، والتي سميت كذلك لقدرتهاعلى الارتباط بأمينات داخلية المنشأ تظهر في الأنسجة بتراكيز نزرة (قليلة). يلعب تار1 دورا في تنظيم النقل العصبي في عصبونات الدوبامين، النورإبينفرين والسيروتونين بالجهاز العصبي المركزي، كما يؤثر على الجهاز المناعي والجهاز المناعي العصبي عبر آليات مختلفة.

تار1 هومستقبل عالي الألفة للأمفيتامين، ميثامفيتامين، دوبامين والأمينات النزرة. تتوسط الأمينات النزرة بعض التأثيرات الخلوية لهذه النواقل العصبية في العصبونات أحادية الأمين في الجهاز العصبي المركزي.

الربائط الأساسية داخلية المنشأ لمستقبل تار1 البشري (hTAAR1) مرتبة حسب الفاعلية هي: تيرامين> فينيثيلامين> دوبامين = أكتوبامين.

مراجع

^ "Entrez Gene: TAAR1 trace amine associated receptor 1". مؤرشف من الأصل في 05 ديسمبر 2010.
↑ Maguire JJ, Davenport AP (20 February 2018). receptor". IUPHAR/BPS Guide to PHARMACOLOGY. International Union of Basic and Clinical Pharmacology. مؤرشف من الأصل في 20 يونيو2019. اطلع عليه بتاريخ 16 يوليو2018.
Tissue Distribution
CNS (region specific) & several peripheral tissues:
Stomach > amygdala, kidney, lung, small intestine > cerebellum, dorsal root ganglion, hippocampus, hypothalamus, liver, medulla oblongata, pancreas, pituitary gland, pontine reticular formation, prostate, skeletal muscle, spleen. ...
Leukocytes ...Pancreatic islet β cells ... Primary Tonsillar B Cells ... Circulating leukocytes of healthy subjects (upregulation occurs upon addition of phytohaemagglutinin).
Species: Human ...
In the brain (mouse, rhesus monkey) the TA1 receptor localises to neurones within the momaminergic pathways and there is emerging evidence for a modulatory role for TA1 on function of these systems. Co-expression of TA1 with the dopamine transporter (either within the same neurone or in adjacent neurones) implies direct/indirect modulation of CNS dopaminergic function. In cells expressing both human TA1 and a monoamine transporter (DAT, SERT or NET) signalling via TA1 is enhanced [26,48,50–51]. ...
Functional Assays ...
Mobilization of internal calcium in RD-HGA16 cells transfected with unmodified human TA1
Response measured: Increase in cytopasmic calcium ...
Measurement of cAMP levels in human cultured astrocytes.
Response measured: cAMP accumulation ...
Activation of leukocytes
Species: Human
Tissue: PMN, T and B cells
Response measured: Chemotactic migration towards TA1 ligands (β-Phenylethylamine, tyramine and 3-iodothyronamine), trace amine induced IL-4 secretion (T-cells) and trace amine induced regulation of T cell marker RNA expression, trace amine induced IgE secretion in B cells.
↑ Grandy DK, Miller GM, Li JX (February 2016). TAARgeting Addiction"-The Alamo Bears Witness to Another Revolution: An Overview of the Plenary Symposium of the 2015 Behavior, Biology and Chemistry Conference". Drug Alcohol Depend. 159: 9–16. doi:10.1016/j.drugalcdep.2015.11.014. PMC 4724540. PMID 26644139. TAAR1 is a high-affinity receptor for METH/AMPH and DA ... This original observation of TAAR1 and DA D2R interaction has subsequently been confirmed and expanded upon with observations that both receptors can heterodimerize with each other under certain conditions ... Additional DA D2R/TAAR1 interactions with functional consequences are revealed by the results of experiments demonstrating that in addition to the cAMP/PKA pathway (Panas et al., 2012) stimulation of TAAR1-mediated signaling is linked to activation of the Ca++/PKC/NFAT pathway (Panas et al.,2012) and the DA D2R-coupled, G protein-independent AKT/GSK3 signaling pathway (Espinoza et al., 2015; Harmeier et al., 2015), such that concurrent TAAR1 and DA DR2R activation could result in diminished signaling in one pathway (e.g. cAMP/PKA) but retention of signaling through another (e.g., Ca++/PKC/NFA)
^ Jing L, Li JX (August 2015). "Trace amine-associated receptor 1: A promising target for the treatment of psychostimulant addiction". Eur. J. Pharmacol. 761: 345–352. doi:10.1016/j.ejphar.2015.06.019. PMC 4532615. PMID 26092759. TAAR1 is largely located in the intracellular compartments both in neurons (Miller, 2011), in glial cells (Cisneros and Ghorpade, 2014) and in peripheral tissues (Grandy, 2007) ... Existing data provided robust preclinical evidence supporting the development of TAAR1 agonists as potential treatment for psychostimulant abuse and addiction. ... Given that TAAR1 is primarily located in the intracellular compartments and existing TAAR1 agonists are proposed to get access to the receptors by translocation to the cell interior (Miller, 2011), future drug design and development efforts may need to take strategies of drug delivery into consideration (Rajendran et al., 2010).
^ Berry MD, Gainetdinov RR, Hoener MC, Shahid M (December 2017). "Pharmacology of human trace amine-associated receptors: Therapeutic opportunities and challenges". Pharmacology & Therapeutics. 180: 161–180. doi:10.1016/j.pharmthera.2017.07.002. PMID 28723415. Outside of the CNS, TAAR1 is mainly expressed in pancreatic β-cells, stomach and intestines in human, rat and mouse (Adriaenssens et al., 2015; Chiellini et al., 2012; Ito et al., 2009; Kidd et al., 2008; Raab et al., 2016; Regard, Sato, & Coughlin, 2008; Revel et al., 2013) (Figure 2). As observed in CNS neurones, TAAR1 in these non-neuronal cells also appears to be primarily intracellular (Raab et al., 2016). ... A sub-population of granulocytes co-express TAAR1 and TAAR2, with evidence for heterodimerization of the two reported (Babusyte et al., 2013).
^ Borowsky B, Adham N, Jones KA, Raddatz R, Artymyshyn R, Ogozalek KL, Durkin MM, Lakhlani PP, Bonini JA, Pathirana S, Boyle N, Pu X, Kouranova E, Lichtblau H, Ochoa FY, Branchek TA, Gerald C (July 2001). "Trace amines: identification of a family of mammalian G protein-coupled receptors". Proceedings of the National Academy of Sciences of the United States of America. 98 (16): 8966–8971. doi:10.1073/pnas.151105198. PMC 55357. PMID 11459929.
^ Bunzow JR, Sonders MS, Arttamangkul S, Harrison LM, Zhang G, Quigley DI, Darland T, Suchland KL, Pasumamula S, Kennedy JL, Olson SB, Magenis RE, Amara SG, Grandy DK (December 2001). "Amphetamine, 3,4-methylenedioxymethamphetamine, lysergic acid diethylamide, and metabolites of the catecholamine neurotransmitters are agonists of a rat trace amine receptor". Molecular Pharmacology. 60 (6): 1181–1188. doi:10.1124/mol.60.6.1181. PMID 11723224.
↑ Miller GM (January 2011). "The emerging role of trace amine-associated receptor 1 in the functional regulation of monoamine transporters and dopaminergic activity". Journal of Neurochemistry. 116 (2): 164–176. doi:10.1111/j.1471-4159.2010.07109.x. PMC 3005101. PMID 21073468.
^ Lindemann L, Ebeling M, Kratochwil NA, Bunzow JR, Grandy DK, Hoener MC (March 2005). "Trace amine-associated receptors form structurally and functionally distinct subfamilies of novel G protein-coupled receptors". Genomics. 85 (3): 372–385. doi:10.1016/j.ygeno.2004.11.010. PMID 15718104.
^ Cisneros IE, Ghorpade A (October 2014). "Methamphetamine and HIV-1-induced neurotoxicity: role of trace amine associated receptor 1 cAMP signaling in astrocytes". Neuropharmacology. 85: 499–507. doi:10.1016/j.neuropharm.2014.06.011. PMC 4315503. PMID 24950453. TAAR1 overexpression significantly decreased EAAT-2 levels and glutamate clearance ... METH treatment activated TAAR1 leading to intracellular cAMP in human astrocytes and modulated glutamate clearance abilities. Furthermore, molecular alterations in astrocyte TAAR1 levels correspond to changes in astrocyte EAAT-2 levels and function.
^ Rogers TJ (2012). "The molecular basis for neuroimmune receptor signaling". J Neuroimmune Pharmacol. 7 (4): 722–724. doi:10.1007/s11481-012-9398-4. PMC 4011130. PMID 22935971.
^ Panas MW, Xie Z, Panas HN, Hoener MC, Vallender EJ, Miller GM (December 2012). "Trace amine associated receptor 1 signaling in activated lymphocytes". Journal of Neuroimmune Pharmacology. 7 (4): 866–876. doi:10.1007/s11481-011-9321-4. PMC 3593117. PMID 22038157.
^ Babusyte A, Kotthoff M, Fiedler J, Krautwurst D (March 2013). "Biogenic amines activate blood leukocytes via trace amine-associated receptors TAAR1 and TAAR2". Journal of Leukocyte Biology. 93 (3): 387–394. doi:10.1189/jlb.0912433. PMID 23315425.