Niacinski receptor 1
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| Niacinski receptor 1 | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Identifikatori | |||||||||||
| Simboli | NIACR1; GPR109A; PUMAG; Puma-g; HM74a; HM74b | ||||||||||
| Vanjski ID | OMIM: 609163 MGI: 1933383 HomoloGene: 4391 IUPHAR: GeneCards: NIACR1 Gene | ||||||||||
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| Ortolozi | |||||||||||
| Vrsta | Čovek | Miš | |||||||||
| Entrez | 338442 | 80885 | |||||||||
| Ensembl | ENSG00000182782 | ENSMUSG00000045502 | |||||||||
| UniProt | Q8TDS4 | Q0VBA6 | |||||||||
| RefSeq (mRNA) | NM_177551 | NM_030701 | |||||||||
| RefSeq (protein) | NP_808219 | NP_109626 | |||||||||
| Lokacija (UCSC) | Chr 12: 121.75 - 121.75 Mb | Chr 5: 124.12 - 124.13 Mb | |||||||||
| PubMed pretraga | [1] | [2] | |||||||||
Niacinski receptor 1, takođe poznat kao NIACR1 ili GPR109A, je protein koji je kod čoveka kodiran NIACR1 genom.[1][2][3][4]
GPR109A receptor ima visok afinitet za nikotinsku kiselinu (niacin)[3][4]. On je član grupe GPCR receptora nikotinske kiseline (drugi član je GPR109B).
GPR109A je Gi / Go protein-spregnuti receptor.[3]
Za GPR109A se smatra da je biomolekulska meta niacina, koji je široko propisivani lek za tretman dislipidemije, i za povišenje nivoa HDL holesterola. Terapeutski učinak niacina je ograničen ispiranjem.[5] Kod GPR109A nokaut miševa, efekti nijacina na lipide[6] i ispiranje[7] su eliminisani. Kod arestin beta 1 nokaut miševa, niacinski efekat na ispiranje je znatno umanjen dok je njegov uticaj na lipidne promene zadržan.[8]
Precizni mehanizam dejstva niacinskih terapeutskih efekata nije potpuno istražen. Smatra se da on delom deluje putem aktivacije GPR109A, što umanjuje nivoe intracelularnog cAMP i time se inhibira lipolizu adipocitima.[9] U kontrastu s tim, efekat ispiranja je posledica GPR109A aktivacije ERK 1/2 MAP kinaza[10] posredovanog arestinom beta 1.[8] Aktivacija MAP kinaza zatim izaziva oslobađanje prostaglandina D2 iz Langerhanovih ćelija kože.[11]
- ↑ Takeda S, Kadowaki S, Haga T, Takaesu H, Mitaku S (June 2002). „Identification of G protein-coupled receptor genes from the human genome sequence”. FEBS Letters 520 (1-3): 97–101. DOI:10.1016/S0014-5793(02)02775-8. PMID 12044878.
- ↑ „Entrez Gene: GPR109A G protein-coupled receptor 109A”.
- ↑ 3,0 3,1 3,2 Wise A, Foord SM, Fraser NJ, Barnes AA, Elshourbagy N, Eilert M, Ignar DM, Murdock PR, Steplewski K, Green A, Brown AJ, Dowell SJ, Szekeres PG, Hassall DG, Marshall FH, Wilson S, Pike NB (March 2003). „Molecular identification of high and low affinity receptors for nicotinic acid”. The Journal of Biological Chemistry 278 (11): 9869–74. DOI:10.1074/jbc.M210695200. PMID 12522134.
- ↑ 4,0 4,1 Soga T, Kamohara M, Takasaki J, Matsumoto S, Saito T, Ohishi T, Hiyama H, Matsuo A, Matsushime H, Furuichi K (March 2003). „Molecular identification of nicotinic acid receptor”. Biochemical and Biophysical Research Communications 303 (1): 364–9. DOI:10.1016/S0006-291X(03)00342-5. PMID 12646212.
- ↑ Pike NB (December 2005). „Flushing out the role of GPR109A (HM74A) in the clinical efficacy of nicotinic acid”. The Journal of Clinical Investigation 115 (12): 3400–3. DOI:10.1172/JCI27160. PMC 1297267. PMID 16322787.
- ↑ Tunaru S, Kero J, Schaub A, Wufka C, Blaukat A, Pfeffer K, Offermanns S (March 2003). „PUMA-G and HM74 are receptors for nicotinic acid and mediate its anti-lipolytic effect”. Nature Medicine 9 (3): 352–5. DOI:10.1038/nm824. PMID 12563315.
- ↑ Benyó Z, Gille A, Kero J, Csiky M, Suchánková MC, Nüsing RM, Moers A, Pfeffer K, Offermanns S (December 2005). „GPR109A (PUMA-G/HM74A) mediates nicotinic acid-induced flushing”. The Journal of Clinical Investigation 115 (12): 3634–40. DOI:10.1172/JCI23626. PMC 1297235. PMID 16322797.
- ↑ 8,0 8,1 Walters RW, Shukla AK, Kovacs JJ, Violin JD, Dewire SM, Lam CM, Chen JR, Muehlbauer MJ, Whalen EJ, Lefkowitz RJ (April 2009). „beta-Arrestin1 mediates nicotinic acid-induced flushing, but not its antilipolytic effect, in mice”. The Journal of Clinical Investigation. DOI:10.1172/JCI36806. PMID 19349687.
- ↑ Zhang Y, Schmidt RJ, Foxworthy P, Emkey R, Oler JK, Large TH, Wang H, Su EW, Mosior MK, Eacho PI, Cao G (August 2005). „Niacin mediates lipolysis in adipose tissue through its G-protein coupled receptor HM74A”. Biochemical and Biophysical Research Communications 334 (2): 729–32. DOI:10.1016/j.bbrc.2005.06.141. PMID 16018973.
- ↑ Richman JG, Kanemitsu-Parks M, Gaidarov I, Cameron JS, Griffin P, Zheng H, Guerra NC, Cham L, Maciejewski-Lenoir D, Behan DP, Boatman D, Chen R, Skinner P, Ornelas P, Waters MG, Wright SD, Semple G, Connolly DT (June 2007). „Nicotinic acid receptor agonists differentially activate downstream effectors”. The Journal of Biological Chemistry 282 (25): 18028–36. DOI:10.1074/jbc.M701866200. PMID 17452318.
- ↑ Tang Y, Zhou L, Gunnet JW, Wines PG, Cryan EV, Demarest KT (June 2006). „Enhancement of arachidonic acid signaling pathway by nicotinic acid receptor HM74A”. Biochemical and Biophysical Research Communications 345 (1): 29–37. DOI:10.1016/j.bbrc.2006.04.051. PMID 16674924.
- „Nicotinic Acid Receptor Family: GPR109A”. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Arhivirano iz originala na datum 2015-02-23.