6가지 사람 미량 아민 관련 수용체(hTAAR) – hTAAR1, hTAAR2, hTAAR5, hTAAR6, hTAAR8, hTAAR9 – 가 식별되었고, 부분적으로 특성화되었다. 아래의 표에는 이러한 수용체의 발현 프로필, 신호전달 메커니즘, 리간드, 생리적 기능에 대한 문헌 검토, 약리학 데이터베이스, 보충적 기본 연구 문서의 요약 정보가 포함되어 있다.
↑ 가나다라마사람을 비롯한 다른 동물의 경우 후각상피에서 발현되는 TAAR은 특정 페로몬을 포함한 휘발성아민냄새 물질을 감지하는 후각 수용체로 기능한다.[9][15] 이들 TAAR은 사회적 신호의 후각 감지에 관여하는 페로몬 수용체의 한 종류로 기능하는 것으로 추정된다.[9][15] 사람이 아닌 동물을 대상으로 한 연구를 검토한 결과, 후각상피의 TAAR이 작용제에 대한 매력적이거나 혐오스러운 행동 반응을 매개할 수 있다는 것이 밝혀졌다.[9] 이 리뷰에서는 또한 TAAR에 의해 유발되는 행동 반응이 종마다 다를 수 있다는 점을 지적했다.[9] 예를 들어, TAAR5는 쥐에서 트라이메틸아민에 대한 이끌림을 매개하고, 래트에서 트라이메틸아민에 대한 혐오감을 매개한다.[9] 사람의 경우 hTAAR5는 hTAAR5 작용제로 작용하는 것으로 알려진 트라이메틸아민에 대한 혐오감을 매개하는 것으로 추정되며, 사람에게 혐오감을 주는 역겨운 생선같은 냄새를 가지고 있다.[9][19] 그러나 hTAAR5는 사람의 트라이메틸아민에 대한 후각을 담당하는 유일한 후각 수용체가 아니다.[9][19] 2015년 12월을 기준으로 hTAAR5에 의한 트라이메틸아민 혐오감은 발표된 연구에서 조사되지 않았다.[19]
↑hTAAR9는 대부분의 개체에서 기능적인 수용체이지만, 사람의 hTAAR9 유전자의 기능상실 돌연변이(특히, 다형성 조기 종결 코돈)는 개체에서 10~30% 정도 발생한다.[12][13]
질병 관련성 및 임상적 중요성
울로타론트/SEP 363856은 조현병에 대한 3상 임상 시험과 파킨슨병 정신병에 대한 초기 임상 시험에 사용된 TAAR1 작용제이다. 이 약은 미국 식품의약국(FDA)로부터 획기적인 치료제로 지정을 받았다.[30][31][32]
↑Bunzow JR, Sonders MS, Arttamangkul S, Harrison LM, Zhang G, Quigley DI, 외. (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. PMID11723224.
↑ 가나다라마바사아자차카타파하거너Liberles SD (October 2015). “Trace amine-associated receptors: ligands, neural circuits, and behaviors”. 《Current Opinion in Neurobiology》 34: 1–7. doi:10.1016/j.conb.2015.01.001. PMC4508243. PMID25616211. Roles for another receptor are supported by TAAR5-independent trimethylamine anosmias in humans [32]. ... Several TAARs detect volatile and aversive amines, but the olfactory system is capable of discarding ligand-based or function-based constraints on TAAR evolution. Particular TAARs have mutated to recognize new ligands, with almost an entire teleost clade losing the canonical amine-recognition motif. Furthermore, while some TAARs detect aversive odors, TAAR-mediated behaviors can vary across species. ... The ability of particular TAARs to mediate aversion and attraction behavior provides an exciting opportunity for mechanistic unraveling of odor valence encoding. Figure 2: Table of ligands, expression patterns, and species-specific behavioral responses for each TAAR
↑ 가나다라마Davenport AP, Alexander SP, Sharman JL, Pawson AJ, Benson HE, Monaghan AE, 외. (July 2013). “International Union of Basic and Clinical Pharmacology. LXXXVIII. G protein-coupled receptor list: recommendations for new pairings with cognate ligands”. 《Pharmacological Reviews》 65 (3): 967–986. doi:10.1124/pr.112.007179. PMC3698937. PMID23686350. TAAR2 and TAAR9 Two of the trace amine receptors are inactivated in a portion of the human population. There is a polymorphism in TAAR2 (rs8192646) producing a premature stop codon at amino acid 168 in 10–15% of Asians. TAAR9 (formerly TRAR3) appears to be functional in most individuals but has a polymorphic premature stop codon at amino acid 61 (rs2842899) with an allele frequency of 10–30% in different populations (Vanti et al., 2003). TAAR3 (formerly GPR57) and TAAR4 (current gene symbol, TAAR4P) are thought to be pseudogenes in man though functional in rodents (Lindemann et al., 2005).
↑ 가나다라마바사아자차카타파Berry 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. PMID28723415.
↑ 가나다라마바사아자차카“Trace amine receptor: Introduction”. International Union of Basic and Clinical Pharmacology. 2014년 2월 23일에 원본 문서에서 보존된 문서. 2014년 2월 15일에 확인함. Importantly, three ligands identified activating mouse Taars are natural components of mouse urine, a major source of social cues in rodents. Mouse Taar4 recognizes β-phenylethylamine, a compound whose elevation in urine is correlated with increases in stress and stress responses in both rodents and humans. Both mouse Taar3 and Taar5 detect compounds (isoamylamine and trimethylamine, respectively) that are enriched in male versus female mouse urine. Isoamylamine in male urine is reported to act as a pheromone, accelerating puberty onset in female mice [34]. The authors suggest the Taar family has a chemosensory function that is distinct from odorant receptors with a role associated with the detection of social cues. ... The evolutionary pattern of the TAAR gene family is characterized by lineage-specific phylogenetic clustering [26,30,35]. These characteristics are very similar to those observed in the olfactory GPCRs and vomeronasal (V1R, V2R) GPCR gene families.
↑ 가나Babusyte 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. PMID23315425.
↑ 가나“TAAR2”. International Union of Basic and Clinical Pharmacology. 2018년 5월 15일에 확인함. Primary Transduction Mechanisms Comments: TAAR2 is found to be coexpressed with Gα proteins. However, the transduction pathway of TAAR2 is yet to be determined.
↑ 가나Khan MZ, Nawaz W (October 2016). “The emerging roles of human trace amines and human trace amine-associated receptors (hTAARs) in central nervous system”. 《Biomedicine & Pharmacotherapy》 83: 439–449. doi:10.1016/j.biopha.2016.07.002. PMID27424325.
↑ 가나다Wallrabenstein I, Singer M, Panten J, Hatt H, Gisselmann G (2015). “Timberol® Inhibits TAAR5-Mediated Responses to Trimethylamine and Influences the Olfactory Threshold in Humans”. 《PLOS ONE》 10 (12): e0144704. Bibcode:2015PLoSO..1044704W. doi:10.1371/journal.pone.0144704. PMC4684214. PMID26684881. While mice produce gender-specific amounts of urinary TMA levels and were attracted by TMA, this odor is repellent to rats and aversive to humans [19], indicating that there must be species-specific functions. ... Furthermore, a homozygous knockout of murine TAAR5 abolished the attraction behavior to TMA [19]. Thus, it is concluded that TAAR5 itself is sufficient to mediate a behavioral response at least in mice. ... Whether the TAAR5 activation by TMA elicits specific behavioral output like avoidance behavior in humans still needs to be examined.
↑“TAAR6”. International Union of Basic and Clinical Pharmacology. 2018년 5월 15일에 확인함. Tissue Distribution Kidney, amygdala, hippocampus; Species: Human; Technique: RT-PCR ... Human brain tissues (with the level of expression descending from hippocampus, substantia nigra, amygdala, frontal cortex to basal ganglia), human fetal liver. Not detected in the cerebellum or placenta.; Species: Human; Technique: RT-PCR
↑“TAAR9”. International Union of Basic and Clinical Pharmacology. 2018년 5월 15일에 확인함. Tissue Distribution Comments ... No expression of TAAR9 was detected by RT-PCR in the Grueneberg ganglion [2]. TAAR9 expression was not detected by Northern blot analysis in thalamus, amygdala, midbrain, hippocampus, putamen, caudate, frontal cortex, pons, prostate, stomach, heart, bladder, small intestine, colon or uterus [4].
“Trace Amine Receptors”. 《IUPHAR Database of Receptors and Ion Channels》. International Union of Basic and Clinical Pharmacology. 2014년 3월 24일에 원본 문서에서 보존된 문서. 2025년 2월 20일에 확인함.
