P.sub.2x receptor DNA and protein sequence

Details P.sub.2x receptor DNA and protein sequence P.sub.2x receptor DNA and protein sequence

1997-01-22

1999-11-16

Spector, Lorraine

Chemistry: molecular biology and microbiology

Micro-organism, tissue cell culture or enzyme using process...

Recombinant dna technique included in method of making a...

536 235, 435325, 4352523, 43525411, 4353201, 530350, C12N 1512, C07K 14705, C07H 2104

Patent

active

059856033

DESCRIPTION:

BRIEF SUMMARY
This invention relates to the P.sub.2 X-purinoceptor, its preparation and uses.
The P.sub.2 X-purinoceptor is a ligand-gated ion channel; that is, the receptor itself forms an ion channel which opens when extracellular adenosine 5'-triphosphate (ATP) binds to the receptor. There are five other classes of neurotransmitter receptors (nicotinic acetylcholine, glutamate, glycine, GABA.sub.A and 5-HT.sub.3); these form a structurally related superfamily of ligand-gated ion channels (Barnard, Trends Biochem. Sci. 17, 368-374, (1992)). The P.sub.2x -receptor now identifies a new family of this type of receptor. The unique structure of this receptor, the widespread distribution of this receptor throughout the body, and the numerous physiological roles this receptor may play, make it an important protein that can be used to identify new, therapeutically effective, compounds for the treatment of a number of pathological states.
In 1929 the eminent physiologist Szent-Gyorgyi described powerful cardiovascular actions of extracellular purine nucleosides (e.g. adenosine) and nucleotides (e.g. ATP) (Drury & Szent-Gyorgyi, J. Physiol. 68 213-237 (1929)), but it was not until 1972 that pharmacological evidence was provided to suggest the existence of distinct receptors for extracellular ATP (ie. that recognise ATP but not adenosine) (Burnstock, Pharmacological Reviews 21 509-581 (1972)). The seminal and subsequent work on this area by Burnstock and colleagues was largely unaccepted throughout the 1970s and early 1980s until the development of a range of relatively selective ligands and techniques for directly measuring ATP release overwhelmingly substantiated Burnstock's hypothesis (Barnard et al., Trends Pharmacol. Sci. 15 67-70 (1994)). In the past four or five years, unequivocal evidence for the role of ATP as a neurotransmitter has been provided for sympathetic control of blood flow to the intestine and smooth muscle tone (contractility) in genitourinary tissue such as vas deferens, bladder and ureter (Barnard et al. (loc. cit.) and Evans & Surprenant, Brit. J. Pharmacol. 106 242-249 (1992)). Substantial indirect evidence also exists for the role of ATP as a neurotransmitter in a number of distinct neurones in the spinal cord, autonomic ganglia and certain nuclei in the central nervous system (Bean, Trends Pharmacol. Sci. 15 67-70 (1992), Evans et al., Nature 357, 503-505 (1992) and Edwards et al., Nature 359 144-147 (1992)).
Purinoceptors are classified as P.sub.1 (adenosine as ligand) and P.sub.2 (ATP as ligand). The P.sub.2 receptors are subclassified into two broad types--those that are 7-transmembrane receptors that couple to G-proteins (P.sub.2Y, P.sub.2U, P.sub.2T, and perhaps P.sub.2Z) and those that form a directly gated ion channel (P.sub.2X). Pharmacological and/or physiological evidence for subtypes of each of these types of receptors exists. The most recent nomenclature for these receptors is shown below.


______________________________________ P.sub.2X P.sub.2Y P.sub.2Z ______________________________________ Type Ligand-gated channel G-protein coupled Non-selective pore Subtype P.sub.2X1, P.sub.2X2, P.sub.2X3 P.sub.2Y1, P.sub.2Y2, P.sub.2Y3 ______________________________________
Various P.sub.2 receptors have previously been cloned. P.sub.2Y1 was cloned by the Barnard/Burnstock group (Webb et al., FEBS Lett. 324 219-225 (1993)) based on homology with other 7-TM G-protein coupled receptors. This group used PCR technology and primers based on conserved domains of the second and sixth transmembrane regions to screen a mammalian brain cDNA library and, with final success, an embryonic chick whole-brain cDNA library.
P.sub.2Y2 /P.sub.2U was cloned by the Julius laboratory (Lustig et al., Proc. Nat'l. Acad. Sci. USA 90 5113-5117 (1993)) by expression cloning in the oocyte from cDNA obtained from a NG108-15 neuroblastoma cell line.
P.sub.2Y3 /P.sub.2T was also obtained by the Barnard/Burnstock group using the same probes and embryonic brain cDNA library used to obtain the P.sub.2 Y1 receptor (Barn

REFERENCES:
Bo et al., J. Biol. Chem., 267, 17581-17587, Sep. 5, 1992.
Saxe et al., Genes & Development, 5, 1-8, 1991.
Lewin, Science, 237, 1570, 1987.
Reeck et al., Cell, 50, 667, 1987.
Harden et al, Annu. Rev. Pharmacol. Toxicol. (1995) 35, 541-79 P.sub.2 -Purinergic Receptors: Subtype-Associated Signaling Responses and Structure.

Affiliated with

Also associated with

Rating

P.sub.2x receptor DNA and protein sequence does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with P.sub.2x receptor DNA and protein sequence, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and P.sub.2x receptor DNA and protein sequence will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-1323242