Table: Molecular pharmacology of P2Y-receptor subtypes, updated version

Ivar von Kügelgen

P2-receptors mediate the actions of extracellular nucleotides such as ATP or UTP. The receptors play a physiological or pathophysiological role in a variety of tissues or cells. This includes vasoconstriction due to sympathetic nerve stimulation, blood platelet aggregation, pain transmission and chloride ion secretion in airway epithelia. Two families of P2-receptors are known: P2X-receptors, which represent a totally new class of ligand-gated ion channels with two transmembrane domains, and P2Y-receptors, which belong to the superfamily of G-protein coupled receptors with seven transmembrane domains (e.g., see the predicted secondary structure of the human P2Y6-receptor).

Updated August 2007.

(see reviews von Kügelgen I, 2006, Pharmacological profiles of cloned mammalian P2Y-receptor subtypes, Pharmacology & Therapeutics 110:415-432. Epub 2005 Oct 28.

and: von Kügelgen I and Wetter A, 2000, Molecular pharmacology of P2Y-receptors, Naunyn-Schmiedeberg´s Archives of Pharmacology 362:310-323; published online DOI 10.1007/s002100000310).

Cloned and functionally expressed P2Y-subtypes:

P2Y1, P2Y2, P2Y3, P2Y4, P2Y6, p2y8, P2Y11, P2Y12, P2Y13, tp2y, P2Y14(UDP-Glucose)

(for nomenclature see comments in von Kügelgen and Wetter, 2000, Naunyn-Schmiedeberg´s Archives of Pharmacology 362:310-323)

P2 Receptor Subtype	Species	Tissue Distribution	Cloned from	Genbank Accession N°	Selected References	Principle Agonists	Selected References	Principle Antagonists (pA2 or pKB)	Selected References
P2Y1 other subtypes	Human	Wide including platelets, heart, skeletal muscle, neuronal tissue, digestive tract	Blood Platelets	AF018284	Jin et al. 1998	2^_Methylthio^_ADP> ADP> 2^_Methylthio^_ATP> ATP	Ayyanathan et al.1996; Janssens et al.1996; Leon et al. 1996; Leon et al.1997; Palmer et al. 1998	MRS2179 (6.75) Reactive blue 2 (6.1) Suramin (5.5) PPADS (5.4-4.9)	O´Grady et al. 1996 Schachter et al. 1996 Moro et al. 1998 Guo et al. 1999
			Whole Blood	AJ006945	Leon et al. 1998 (direct submission)
			Erythro leukaemia cells	NM_002563	Ayyanathan et al. 1996
			Genomic DNA	S81950	Janssens et al. 1996
			Erythro leukaemia cells	U42029	Ayyanathan et al. 1996
			Erythro leukaemia cells	U42030	Ayyanathan et al. 1996
			Placenta	Z49205	Leon et al. 1996
	Mouse	See above	Insulinoma cells	U22829	Tokuyama et al. 1995	2^_Methylthio^_ATP> 2-Chloro-ATP > ATP	Tokuyama et al. 1995	No data	No data
			Embryonic stem cells	AJ245636	Leon 1999 (direct submission)
	Rat	See above	Insulinoma cells	U22830	Tokuyama et al. 1995	2^_Methylthio^_ADP = 2^_Methylthio^_ATP > ADP > ATP	Tokuyama et al. 1995; Vöhringer et al. 2000	PPADS (5.5)	Schachter et al. 1997
	Bovine	See above	Corpus Callosum, glial cells	U34041	Matute et al. 1993	2^_Methylthio^_ATP > ATP	Henderson et al. 1995	No data	No data
			Aortic endothelial cells	X87628	Henderson et al. 1995
	Chicken	See above	Brain	X73268	Webb. et al. 1993	2^_Methylthio^_ATP > ATP > ADP	Webb et al. 1993	Suramin (decrease by 100 % at 100 µM) Reactive blue 2 (decrease by 100 % at 100 µM)	Simon et al. 1995
	Turkey	See above	Brain	U09842	Filtz et al. 1994	2^_Methylthio^_ATP > ATP > ADP	Filtz et al. 1994	MRS2179 (6.99) PPADS (5.98) Suramin (5.75)	Boyer et al. 1998
P2Y2 other subtypes	Human	Wide including lung, heart, skeletal muscle, spleen, kidney	Airway epithelium, epithelial cell, CF/T43 cells	NM_002564	Parr et al. 1994	UTP = ATP > Ap4A > ATP	Parr et al. 1994; Lazarowski et al. 1995; Nicholas et al. 1996	Suramin (4.3)	Charlton et al. 1996a Charlton et al. 1996b
			Airway epithelium, epithelial cell, CF/T43 cells	U07225	Parr et al. 1994
	Mouse	See above	Neuro-blastoma cells, NG108-15 cells	L14751	Lustig et al. 1993	UTP = ATP > Ap4A	Lustig et al. 1993	No data	No data
	Rat	See above	Pituitary	L46865	Chen et al. 1996	UTP = ATP	Rice et al. 1995; Chen et al. 1996	No data	No data
			Alveolar type II cell	U09402	Rice et al. 1995
			Smooth muscle cell cDNA library	U56839	Seye et al. 1997
P2Y3 other subtypes	Chicken	Spleen, kidney, CNS	Brain	X98283	Webb et al. 1996	ADP > UTP > UDP	Webb et al. 1996a	Reactive blue 2 (decrease by 100 % at 100 µM) Suramin (5.4)	Webb et al. 1996a
	Turkey	See above	Genomic DNA	AF069555	Li et al. 1998	UDP > 5-Bromo-UDP > 2^_Methylthio^_ADP > ADP	Li et al. 1998	No data	No data
P2Y4 other subtypes	Human	Placenta, lung, vascular smooth muscle	Genomic DNA	NM_002565	Communi et al. 1995	UTP > UTPgS >> ATP, UDP	Communi et al. 1995; Communi et al.1996a; Nguyen et al. 1995; Nicholas et al. 1996	PPADS (decrease by 30-73 % at 100 µM) Reactive blue 2 (decrease by 33 % at 100 µM)	Charlton et al. 1996b Communi et al. 1996a
			Chromosome X	U40223	Nguyen et al. 1995
			Genomic DNA	X91852	Communi et al. 1995
			Pancreas	X96597	Stam et al. 1996
	Rat	See above	Brain	Y11433	Webb et al. 1998	UTP = ATP = ITP = Ap4A	Bogdanov et al. 1998; Webb et al. 1998	Reactive blue 2 (decrease by 100 % at 100 µM)	Bogdanov et al. 1998
			Liver	Y14705	Bogdanov et al. 1997 (direct submission)
	Mouse	See above	N.I.	AJ277752	Suarez-Huerta et al. 2000 (direct submission)	No data	No data	No data	No data
			N.I.	NM_020621	Suarez-Huerta et al. 2000 (direct submission)
P2Y6 other subtypes	Human	Wide including lung, heart, aorta, spleen, placenta, thymus, intestine, brain	Placenta	AF007891	Maier et al. 1997	UDP = 5-Bromo-UDP >> UTP > 2^_Methylthio^_ADP	Communi et al.1996b; Southey et al. 1996; Maier et al. 1997	Reactive blue 2 (6.0) PPADS (decrease by 69 % at 100 µM)	Robaye et al. 1997
			Placenta	AF007892	Maier et al. 1997
			Placenta	AF007893	Maier et al. 1997
			Placenta	NM_004154	Maier et al. 1997
			Stimulated T-lymphocyte	U52464	Hammet et al. 1996 (direct submission)
			N.I.	X97058	Communi et al. 1996 (direct submission)
	Rat	See above	Aortic smooth muscle cells	D63665	Chang et al. 1995	UDP > UTP > ADP > 2^_Methylthio^_ATP	Chang et al. 1995; Nicholas et al. 1996	Reactive blue 2 (decrease by 77 % at 100 µM)	Chang et al. 1995 Boyer et al. 1998
p2y8 other subtypes	Xenopus laevis	Neural plate	Neural plate	X99953	Bogdanov et al. 1997	UTP = CTP = ATP = ITP = GTP	Bogdanov et al. 1997	Suramin (decrease by 100 % at 100 µM)	Bogdanov et al. 1997
P2Y11 other subtypes	Human	Spleen, intestine, immunocytes	Placenta	AF030335	Communi et al. 1997	ATPgS = Benzoyl-Benzoyl-ATP > ATP > 2^_Methylthio^_ATP	Communi et al. 1997; Communi et al. 1999	Suramin (6.09) Reactive blue 2 (decrease by 80 % at 100 µM)	Communi et al. 1999
			Placenta	NM_002566	Communi et al. 1997
P2Y12 other subtypes	Human	Platelets, brain	Platelets	AF313449 AF321815 AB052684 AJ320495	Hollopeter et al. 2001, Takasaki et al. 2001, Zhang et al. 2001	2^_Methylthio^_ADP > ADP	Hollopeter et al. 2001, Takasaki et al. 2001, Zhang et al. 2001	AR-C69931MX >> 2^_Methylthio-AMP	Hollopeter et al. 2001, Takasaki et al. 2001, Zhang et al. 2001
	Rat	See above	Platelets	AF313450	Hollopeter et al. 2001	See above	Hollopeter et al. 2001	2^_Methylthio-AMP	Hollopeter et al. 2001
P2Y13 other subtypes	Human	Spleen, leucocytes, bone marrow, placenta, liver, brain	Spleen, neutrophil granulocytes	NM 023914 variant: NM 176894	Communi et al. 2001, Zhang et al. 2002	2^_Methylthio^_ADP = ADP > ADPbS > IDP	Communi et al. 2001, Zhang et al. 2002	No blockade by MRS2179 3 µM	Zhang et al. 2002
	Mouse	Spleen, leucocytes, liver, brain	Spleen	NM 028808	Zhang et al. 2002	2^_Methylthio^_ADP = ADP = ADPbS = IDP	Zhang et al. 2002	No data	No data
tp2y other subtypes	Turkey	No data	Blood	AF031897	Boyer et al. 1997	UTP = ATP > Ap4A > ATPgS	Boyer et al. 1997; 2000	No data	No data
P2Y14* other subtypes	Human	No data	Myeloblast	NM_014879	Chambers et al. 2000	UDP-Glucose	Chambers et al. 2000	No data	No data
	Rat	No data	N.I.	U76206	Charlton et al. 1997	UDP-Glucose		No data	No data

Ap4A, diadenosine-tetraphosphate; ATPgS, adenosine-thiotriphosphate; N.I., no information; UTPgS, uridine-thiotriphosphate.

* The P2Y14-receptor was previously named UDP-Glucose receptor (for nomenclature see Abbracchio et al., 2003, Trends Pharmacol Sci 24:52-55)

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