Adenozinski A₁ receptor

Adenozinski A1 receptor
Identifikatori
Simboli	ADORA1; RDC7
Vanjski ID	OMIM: 102775 MGI: 99401 HomoloGene: 20165 IUPHAR: A1 GeneCards: ADORA1 Gene
Ontologija gena
Molekularna funkcija	• aktivnost rodopsinu-sličnog receptora; • aktivnost A1 adenozinskog receptora, G-protein spregnutog; • receptorska aktivnost;
Celularna komponenta	• integralno sa ćelijskom membranom; • membrana;
Biološki proces	• fagocitoza; • inflamatorni respons; • prenos signala; • signalni put G-protein spregnutog receptora; • interćelijska signalizacija; • razvoj nervnog sistema; • indukcija apoptoze ekstracelularnim signalima;
Pregled RNK izražavanja
	podaci
Ortolozi

edit

Adenozinski A₁ receptor^[1] je član grupe adenozinskih receptgora, G protein-spregnutih receptora čiji endogeni ligand je adenozin.

Biohemija

A₁ receptori učestvuju u promovisanju sna putem inhibicije holinergičkih neurona bazalnog prednjeg mozga.^[2] A₁ receptori su takođe prisutni u glatkim mišićima širom vaskularnog sistema.^[3]

Signalizacija

Aktivacija adenozinskog A₁ receptora agonistom uzrokuje vezivanje G_i1/2/3 ili G_o proteina. Vezivanje G_i1/2/3 proteina izaziva inhibiciju adenilat ciklaze, i stoga umanjenje cAMP koncentracije. Povišenje koncentracije inozitol-trifosfata/diacilglicerola je posledica aktivacije fosfolipaze C, dok je elevacija nivoa arahidonske kiseline posredovano DAG lipazom, koja odvaja DAG i formira arahidonsku kiselinu.

Nekoliko tipova kalijumskih kanala se aktivira, dok se N-, P-, i Q-tipovi kalcijumskih kanala inhibiraju.^[4]

Mehanizam

Ovaj receptor ima inhibitornu funkciju na većinu tkiva. U mozgu, on usporava metaboličku aktivnost kombinacijom dejstava. Presonaptički, on redukuje otpuštanje iz sinaptičkih vezikula.

Ligandi

Kofein, kao i teofilin, su antagonisti A₁ i A_2A receptora u mozgu.

Agonisti

2-hloro-N(6)-ciklopentil adenozin (CCPA).
N6-ciklopentiladenozin
N(6)-cikloheksiladenozin

Antagonisti

Neselektivni

Selektivni

8-Ciklopentil-1,3-dimetilksantin (CPX / 8-ciklopentil teofilin)
8-Ciklopentyl-1,3-dipropil ksantin (DPCPX)
8-Fenil-1,3-dipropilksantin
Bamifillin
BG-9719^[5]
BG-9928^[6]
FK-453
FK-838
Rolofilin (KW-3902)^[7]^[8]
N-0861

Literatura

↑ Townsend-Nicholson A, Baker E, Schofield PR, Sutherland GR (1995). „Localization of the adenosine A₁ receptor subtype gene (ADORA1) to chromosome 1q32.1”. Genomics 26 (2): 423–5. DOI:10.1016/0888-7543(95)80236-F. PMID 7601478.
↑ Elmenhorst D, Meyer PT, Winz OH, Matusch A, Ermert J, Coenen HH, Basheer R, Haas HL, Zilles K, Bauer A (2007). „Sleep deprivation increases A₁ adenosine receptor binding in the human brain: a positron emission tomography study”. J. Neurosci. 27 (9): 2410–5. DOI:10.1523/JNEUROSCI.5066-06.2007. PMID 17329439.
↑ Tawfik HE, Schnermann J, Oldenburg PJ, Mustafa SJ (2005). „Role of A₁ adenosine receptors in regulation of vascular tone”. Am. J. Physiol. Heart Circ. Physiol. 288 (3): H1411–6. DOI:10.1152/ajpheart.00684.2004. PMID 15539423.
↑ Fredholm BB, IJzerman AP, Jacobson KA, Klotz KN, Linden J (December 2001). „International Union of Pharmacology. XXV. Nomenclature and classification of adenosine receptors”. Pharmacol. Rev. 53 (4): 527–52. PMID 11734617.
↑ Gottlieb SS, Brater DC, Thomas I, Havranek E, Bourge R, Goldman S, Dyer F, Gomez M, Bennett D, Ticho B, Beckman E, Abraham WT (March 2002). „BG9719 (CVT-124), an A1 adenosine receptor antagonist, protects against the decline in renal function observed with diuretic therapy”. Circulation 105 (11): 1348–53. DOI:10.1161/hc1102.105264. PMID 11901047.
↑ Greenberg B, Thomas I, Banish D, Goldman S, Havranek E, Massie BM, Zhu Y, Ticho B, Abraham WT (August 2007). „Effects of multiple oral doses of an A1 adenosine antagonist, BG9928, in patients with heart failure: results of a placebo-controlled, dose-escalation study”. Journal of the American College of Cardiology 50 (7): 600–6. DOI:10.1016/j.jacc.2007.03.059. PMID 17692744.
↑ Givertz MM, Massie BM, Fields TK, Pearson LL, Dittrich HC (October 2007). „The effects of KW-3902, an adenosine A1-receptor antagonist,on diuresis and renal function in patients with acute decompensated heart failure and renal impairment or diuretic resistance”. Journal of the American College of Cardiology 50 (16): 1551–60. DOI:10.1016/j.jacc.2007.07.019. PMID 17936154.
↑ Cotter G, Dittrich HC, Weatherley BD, Bloomfield DM, O'Connor CM, Metra M, Massie BM (October 2008). „The PROTECT pilot study: a randomized, placebo-controlled, dose-finding study of the adenosine A1 receptor antagonist rolofylline in patients with acute heart failure and renal impairment”. Journal of Cardiac Failure 14 (8): 631–40. DOI:10.1016/j.cardfail.2008.08.010. PMID 18926433.

Spoljašnje veze

„Adenosine Receptors: A₁”. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Arhivirano iz originala na datum 2020-09-20.
MeSH Adenosine A1 Receptor

[pmid7601478-1] Townsend-Nicholson A, Baker E, Schofield PR, Sutherland GR (1995). „Localization of the adenosine A₁ receptor subtype gene (ADORA1) to chromosome 1q32.1”. Genomics 26 (2): 423–5. DOI:10.1016/0888-7543(95)80236-F. PMID 7601478.

[pmid17329439-2] Elmenhorst D, Meyer PT, Winz OH, Matusch A, Ermert J, Coenen HH, Basheer R, Haas HL, Zilles K, Bauer A (2007). „Sleep deprivation increases A₁ adenosine receptor binding in the human brain: a positron emission tomography study”. J. Neurosci. 27 (9): 2410–5. DOI:10.1523/JNEUROSCI.5066-06.2007. PMID 17329439.

[pmid15539423-3] Tawfik HE, Schnermann J, Oldenburg PJ, Mustafa SJ (2005). „Role of A₁ adenosine receptors in regulation of vascular tone”. Am. J. Physiol. Heart Circ. Physiol. 288 (3): H1411–6. DOI:10.1152/ajpheart.00684.2004. PMID 15539423.

[pmid11734617-4] Fredholm BB, IJzerman AP, Jacobson KA, Klotz KN, Linden J (December 2001). „International Union of Pharmacology. XXV. Nomenclature and classification of adenosine receptors”. Pharmacol. Rev. 53 (4): 527–52. PMID 11734617.

[pmid11901047-5] Gottlieb SS, Brater DC, Thomas I, Havranek E, Bourge R, Goldman S, Dyer F, Gomez M, Bennett D, Ticho B, Beckman E, Abraham WT (March 2002). „BG9719 (CVT-124), an A1 adenosine receptor antagonist, protects against the decline in renal function observed with diuretic therapy”. Circulation 105 (11): 1348–53. DOI:10.1161/hc1102.105264. PMID 11901047.

[pmid17692744-6] Greenberg B, Thomas I, Banish D, Goldman S, Havranek E, Massie BM, Zhu Y, Ticho B, Abraham WT (August 2007). „Effects of multiple oral doses of an A1 adenosine antagonist, BG9928, in patients with heart failure: results of a placebo-controlled, dose-escalation study”. Journal of the American College of Cardiology 50 (7): 600–6. DOI:10.1016/j.jacc.2007.03.059. PMID 17692744.

[pmid17936154-7] Givertz MM, Massie BM, Fields TK, Pearson LL, Dittrich HC (October 2007). „The effects of KW-3902, an adenosine A1-receptor antagonist,on diuresis and renal function in patients with acute decompensated heart failure and renal impairment or diuretic resistance”. Journal of the American College of Cardiology 50 (16): 1551–60. DOI:10.1016/j.jacc.2007.07.019. PMID 17936154.

[pmid18926433-8] Cotter G, Dittrich HC, Weatherley BD, Bloomfield DM, O'Connor CM, Metra M, Massie BM (October 2008). „The PROTECT pilot study: a randomized, placebo-controlled, dose-finding study of the adenosine A1 receptor antagonist rolofylline in patients with acute heart failure and renal impairment”. Journal of Cardiac Failure 14 (8): 631–40. DOI:10.1016/j.cardfail.2008.08.010. PMID 18926433.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]