5-HT6 수용체

5-HT6 receptor
HTR6
식별자
별칭HTR6, 5-HT6, 5-HT6R, 5-HT6 수용체, 5-HT6 수용체, 5-히드록시트리프타민 수용체 6
외부 IDOMIM: 601109 MGI: 1196627 호몰로진: 673 GeneCard: HTR6
직교체
종인간마우스
엔트레스

3362

15565

앙상블

ENSG00000158748

ENSMUSG00000028747

유니프로트

P50406

Q9R1C8

RefSeq(mRNA)

NM_000871

NM_021358
NM_001377096

RefSeq(단백질)

NP_000862

NP_067333
NP_001364025

위치(UCSC)Chr 1: 19.66 – 19.68MbChr 4: 139.06 – 139.08Mb
PubMed 검색[3][4]
위키다타
인간 보기/편집마우스 보기/편집

5HT6 수용체는 내생 신경전달물질 세로토닌(5-hydroxytryptamine, 5HT)을 결합하는 5HT 수용체 아종이다.[5] G와s 결합하여 흥분성 신경전달물질을 매개하는 G단백질결합수용체(GPCR)이다.[5] HTR6는 수용체에 대한 인간 유전자 인코딩을 나타낸다.[6]

분배

5HT6 수용체는 거의 전적으로 뇌에서 발현된다.[7] 후각결절, 대뇌피질(전방 및 엔토르히날 영역), 측핵, 선조체, 가오산핵, 해마, 소뇌 분자층을 포함한 다양한 영역에 분포한다.[5][8][9] 외사성, 변연성, 피질성 부위의 풍부함을 바탕으로6 5HT 수용체가 운동 제어, 감정성, 인지, 기억력 등의 기능에서 역할을 한다고 제안할 수 있다.[7][9][10]

함수

중앙 5HT6 수용체 봉쇄는 다양한 뇌 영역에서 글루타마마테라믹과 콜린거 신경전달을 증가시키는 반면,[11][12][13][14] 활성화는 GABAergic 신호를 광범위하게 증가시키는 것으로 나타났다.[15] 5HT6 수용체들의 대항작용도 전두피질에서 도파민과 노르에피네프린 분비를 촉진시키는 반면 자극은 정반대의 효과를 가진다.[14][16][15]

적대자들에 대한 마약 타겟으로

5HT6 수용체에는 기능적으로 흥분 작용이 있지만 GABAergic 뉴런과 대체로 공동 국부화되어 있어 전반적인 뇌 활동 억제를 발생시킨다.[15] 이와 병행하여 5HT6 길항자는 인식, 학습, 기억력을 향상시키기 위해 가설을 세운다.[17] 라트레피르딘, 이달로피르딘(Lu AE58054), 인테피르딘(SB-742,457/RVT-101) 등의 작용제를 알츠하이머병 등 치매의 새로운 치료법으로 평가했다.[14][18][19] 그러나 라트레피르딘, 이달로피르딘, 인테피르딘의 3단계 실험은 효과를 입증하는 데 실패했다.

5HT6 대항제 역시 식욕저하와 체중감소를 유발하는 것으로 나타났으며, 그 결과 PRX-07034, BVT-5,182, BVT-74,316이 비만 치료제로 조사되고 있다.[20][21]

고통받는 사람들을 위한 약물 타겟으로

최근 5HT의6 작용제인 WAY-181,187과 WAY-208,466이 우울증, 불안, 강박장애(OCD)의 설치류 모델에서 활발히 활동하고 있는 것으로 나타났으며, 그러한 작용제는 이러한 조건에 유용한 치료법이 될 수 있다.[15][22] 추가적으로, 간접적인 5HT6 활성화는 선택적 세로토닌 재흡수 억제제(SSRIs)와 삼순환 항우울제(TCAs)와 같은 세로토닌 항우울제의 치료적 편익에 역할을 할 수 있다.[citation needed]

리간즈

많은 수의 선택적6 5HT 리간드가 개발되었다.[23][24][25][26][27][28][29][30][31]

고민자

완전고충인자

부분작용제

  • E-6801[34]
  • E-6837 - 랫드 5-HT6 수용체에서 부분작용제. 쥐에서 구강 활성이며, 만성[35] 투여로 체중 감소를 유발
  • EMD-386,088 - 강력한 부분작용제(EC50 = 1nM)이지만 선택성이[36][37] 없음
  • LSD - Emax = 60%[38]

적대자와 역작용제

유전학

HTR6 유전자의 다형성은 신경정신과 질환과 관련이 있다. 예를 들어, C267T (rs1805054) 다형성과 알츠하이머병 사이의 연관성이 나타났다.[45] 다른 사람들은 파킨슨병과 관련된 다형성을 연구했다.[46]

참고 항목

참조

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