P2Y receptor

P2Y receptori su familija purinskih receptora, G protein-spregnutih receptora koje stimulišu nukleotidi poput ATP, ADP, UTP, UDP i UDP-glukoza. Do sada, 12 ljudskih P2Y receptora je bilo klonirano: P2Y₁, P2Y₂, P2Y₄, P2Y₅, P2Y₆, P2Y₈, P2Y₉ (ili GPR23), P2Y₁₀, P2Y₁₁, P2Y₁₂, P2Y₁₃ i P2Y₁₄.^[1]

P2Y receptori su prisutni u skoro svim ljudskim tkivima. Oni ispoljavaju brojne biološke funkcije koje su bazirane na njihovim G-protein spregama.

Sprege

Biološki efekti aktivacije P2Y receptora su zavisni od načina na koji su spregnuti u nizvodnim signalnim putevima, bili putem G_i, G_q/11 ili G_s G proteini. Ljudski P2Y receptori imaju sledeće G protein sprege:

Protein	Gen	Sprega	Nukleotid
P2RY₁	P2RY1	G_q/11	ADP
P2RY₂	P2RY2	G_q/11	ATP, UTP
P2RY₄	P2RY4	G_i i G_q/11	UTP
P2RY₅ / LPA₆	LPAR6		Lizofosfatidna kiselina^[2]
P2RY₆	P2RY6	G_q/11	UDP
P2RY₈	P2RY8		orfan receptor
P2RY₉ / LPAR₄ / GPR23	LPAR4		Lizofosfatidna kiselina
P2RY₁₀	P2RY10		orfan receptor
P2RY₁₁	P2RY11	G_s i G_q/11	ATP
P2RY₁₂	P2RY12	G_i	ADP
P2RY₁₃	P2RY13	G_i	ADP
P2RY₁₄	P2RY14	G_q/11	UDP-glukoza

Brojevi P2Y receptora nisu konsekutivni zato što se za nekoliko receptora (P2Y₃, P2Y₅, P2Y₇, P2Y₈, P2Y₉, P2Y₁₀) mislilo da su P2Y receptori kad su klonirani, dok oni to zapravo nisu.

P2Y₃ je avijarni homolog sisarskog P2Y₆ receptora.^[3]

Klinički značaj

P2Y₂ je potencijalni cilj za lečenje cistične fibroze.^[4]

P2Y₁₁ je regulator imunskih odgovora. Rasprostranjeni polimorfizam ovog gena, koji je prisutan kod skoro 20% ljudi Severno Evropskog porekla, doprinosi povećanom riziku miokardijalne infarkcije. Iz tog razloga je P2Y₁₁ interesantna proteinska meta za razvoj lekova za lečenje miokardijalne infarkcije.^[5]

Na P2Y₁₂ dejstvuje antitrombocitni lek klopidogrel^[6] i drugi tienopiridini.

Reference

↑ Abbracchio MP, Burnstock G, Boeynaems JM, Barnard EA, Boyer JL, Kennedy C, Knight GE, Fumagalli M, Gachet C, Jacobson KA, Weisman GA (2006). „International Union of Pharmacology LVIII: update on the P2Y G protein-coupled nucleotide receptors: from molecular mechanisms and pathophysiology to therapy”. Pharmacol. Rev. 58 (3): 281–341. DOI:10.1124/pr.58.3.3. PMID 16968944.
↑ Pasternack SM, von Kügelgen I, Aboud KA, Lee YA, Rüschendorf F, Voss K, Hillmer AM, Molderings GJ, Franz T, Ramirez A, Nürnberg P, Nöthen MM, Betz RC (2008). „G protein-coupled receptor P2Y5 and its ligand LPA are involved in maintenance of human hair growth”. Nature Genetics 40 (3): 329-34. PMID 18297070.
↑ Li Q, Olesky M, Palmer RK, Harden TK, Nicholas RA. (1998). „Evidence that the p2y3 receptor is the avian homologue of the mammalian P2Y6 receptor”. Mol Pharmacol 54 (3): 541–6. PMID 9730913.
↑ Kellerman D, Evans R, Mathews D, Shaffer C (2002). „Inhaled P2Y₂ receptor agonists as a treatment for patients with Cystic Fibrosis lung disease”. Adv. Drug Deliv. Rev. 54 (11): 1463–74. DOI:10.1016/S0169-409X(02)00154-0. PMID 12458155.
↑ Amisten S, Melander O, Wihlborg AK, Berglund G, Erlinge D (2007). „Increased risk of acute myocardial infarction and elevated levels of C-reactive protein in carriers of the Thr-87 variant of the ATP receptor P2Y₁₁”. Eur. Heart J. 28 (1): 13–8. DOI:10.1093/eurheartj/ehl410. PMID 17135283.
↑ Herbert JM, Savi P (2003). „P2Y12, a new platelet ADP receptor, target of clopidogrel”. Seminars in vascular medicine 3 (2): 113–22. DOI:10.1055/s-2003-40669. PMID 15199474.

Literatura

Ivar von Kügelgen: Pharmacology of mammalian P2X- and P2Y-receptors, BIOTREND Reviews No. 03, September 2008,© 2008 BIOTREND Chemicals AG Arhivirano 2009-05-21 na Wayback Machine-u
„P2Y Receptors”. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Arhivirano iz originala na datum 2016-03-03.

Vanjske veze

MeSH Purinergic+P2+receptors

[pmid16968944-1] Abbracchio MP, Burnstock G, Boeynaems JM, Barnard EA, Boyer JL, Kennedy C, Knight GE, Fumagalli M, Gachet C, Jacobson KA, Weisman GA (2006). „International Union of Pharmacology LVIII: update on the P2Y G protein-coupled nucleotide receptors: from molecular mechanisms and pathophysiology to therapy”. Pharmacol. Rev. 58 (3): 281–341. DOI:10.1124/pr.58.3.3. PMID 16968944.

[2] Pasternack SM, von Kügelgen I, Aboud KA, Lee YA, Rüschendorf F, Voss K, Hillmer AM, Molderings GJ, Franz T, Ramirez A, Nürnberg P, Nöthen MM, Betz RC (2008). „G protein-coupled receptor P2Y5 and its ligand LPA are involved in maintenance of human hair growth”. Nature Genetics 40 (3): 329-34. PMID 18297070.

[3] Li Q, Olesky M, Palmer RK, Harden TK, Nicholas RA. (1998). „Evidence that the p2y3 receptor is the avian homologue of the mammalian P2Y6 receptor”. Mol Pharmacol 54 (3): 541–6. PMID 9730913.

[pmid12458155-4] Kellerman D, Evans R, Mathews D, Shaffer C (2002). „Inhaled P2Y₂ receptor agonists as a treatment for patients with Cystic Fibrosis lung disease”. Adv. Drug Deliv. Rev. 54 (11): 1463–74. DOI:10.1016/S0169-409X(02)00154-0. PMID 12458155.

[pmid17135283-5] Amisten S, Melander O, Wihlborg AK, Berglund G, Erlinge D (2007). „Increased risk of acute myocardial infarction and elevated levels of C-reactive protein in carriers of the Thr-87 variant of the ATP receptor P2Y₁₁”. Eur. Heart J. 28 (1): 13–8. DOI:10.1093/eurheartj/ehl410. PMID 17135283.

[pmid15199474-6] Herbert JM, Savi P (2003). „P2Y12, a new platelet ADP receptor, target of clopidogrel”. Seminars in vascular medicine 3 (2): 113–22. DOI:10.1055/s-2003-40669. PMID 15199474.

[1]

[2]

[3]

[4]

[5]

[6]