Disease relevance of P2rx1

• Several P2X receptor subunits were recently cloned; of these, one was cloned from the rat vas deferens (P2X1) and another from pheochromocytoma (PC12) cells differentiated with nerve growth factor (P2X2) [1].
• Selective modulation of ligand-gated P2X purinoceptor channels by acute hypoxia is mediated by reactive oxygen species [2].
• P2X1 receptor subunit immunoreactivity and ATP-evoked fast currents in adult rat dorsal root ganglion neurons [3].
• Increase in cardiac P2X1-and P2Y2-receptor mRNA levels in congestive heart failure [4].
• Short-term hyperthyroidism modulates the fat-cell adenylate cyclase system at the receptor level (beta-receptor number increased, R-site purinergic-receptor number decreased) and the catalytic subunit of adenylate cyclase [5].

Psychiatry related information on P2rx1

• P2X3 receptor blockade raised the pressure and volume thresholds for the reflex, whereas P2X1 receptor blockade diminished motor activity associated with voiding [6].

High impact information on P2rx1

• A P2X purinoceptor expressed by a subset of sensory neurons [7].
• There is sequence similarity between the ATP receptor and RP-2, a gene activated in thymocytes undergoing programmed cell death [8].
• These data provide compelling new evidence indicating that tubuloglomerular feedback signals are coupled to autoregulatory preglomerular vasoconstriction through ATP-mediated activation of P2X1 receptors [9].
• Afferent arterioles from rats and P2X1 KO mice were examined using the juxtamedullary nephron technique [9].
• Sensitivity to two of these antagonists (pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid and pyridoxal 5-phosphate) is restored by replacement of Glu249 by lysine, which occurs at the equivalent position in P2X1 and P2X2 receptors [10].

Chemical compound and disease context of P2rx1

• ATP receptor-mediated increase of Ca ionophore-stimulated arachidonic acid release from PC12 pheochromocytoma cells [11].
• We conclude that NTS A2a-purinoceptor activation evokes differential sympathetic responses similar to those observed during hemorrhage, whereas P2x-purinoceptor and glutamate-receptor activation evokes differential inhibition of sympathetic outputs similar to arterial baroreflex responses [12].
• These results indicate that the impaired autoregulatory response observed in Ang II-dependent hypertension can be attributed to impairment of P2X1 receptor-mediated signal transduction [13].

Biological context of P2rx1

• RP-2 and RP-8 are no longer detectable after 6 h postinduction, when apoptosis and mRNA degradation are evident in the culture [14].
• Sequence analysis of RP-8 cDNA indicates the presence of a zinc finger domain suggestive of a possible DNA regulatory role for the RP-8 protein. cDNA sequence results on RP-2 classify the corresponding protein as an integral membrane protein [14].
• The potency of compound 3 at the recombinant P2X1 receptor (IC50 10.2 +/- 2.6 microM) was lower than PPADS (IC50 98.5 +/- 5.5 nM) or iso-PPADS (IC50 42.5 +/- 17.5 nM), although unlike PPADS its effect was reversible with washout and surmountable [15].
• In the excretory ducts of the testis (ductus epididymidis, vas deferens and its associated seminal vesicles), the major signals were seen with antibodies to P2X1 and P2X2 in the membranes of the smooth muscle layer, suggesting that these receptors are involved in the process of sperm transport and ejaculation [16].
• These results indicate that the 27-amino-acid sequence (175-201) is important for protein trafficking to the membrane and for the formation of a functional P2X1 receptor [17].

Anatomical context of P2rx1

• Similar (heteromeric) P2X subunits also formed trimers, as shown for co-expressed P2X1 and P2X2 subunits, which assembled efficiently to a P2X1+2 receptor that was exported to the plasma membrane [18].
• In the present study, antibodies recognizing the subunits P2X1-P2X7 were applied together with the astroglial marker S100beta and nuclear labeling with Hoechst 33342 to investigate semiquantitatively the distribution of the whole set of P2X receptors in astrocytes of the juvenile rat hippocampus [19].
• RESULTS: In both the bladder detrusor muscle and the ureteral muscle (as well as the accompanying arteries) P2X1 immunoreactivity was associated with the smooth muscle membranes [20].
• Taken together, these results indicate that noradrenergic terminals of the rat hippocampus are equipped with presynaptic facilitatory P2X receptors, displaying a pharmacological profile similar to homomeric P2X1 and P2X3 receptors [21].
• MATERIALS AND METHODS: Distribution of P2X receptor subtypes in rat bladder and ureter has been investigated using specific polyclonal antibodies to P2X1 through to P2X7 receptor subtypes with immunohistochemical methods [20].

Associations of P2rx1 with chemical compounds

• However, none of the currently used P2X purinoceptor antagonists suramin, reactive blue 2 and PPADS blocked ATP evoked currents; in contrast their application resulted in potentiation of the agonist response [22].
• All VRL1-immunoreactive cells and processes colocalized with somatostatin and purinergic P2X1 receptor-IR but not with tyrosine hydroxylase-IR [23].
• However contractions evoked by potassium chloride (60 mm) were unaffected by methyl-beta-cyclodextrin and the inactive analogue alpha-cyclodextrin had no effect on P2X1 receptor-mediated currents or contractions [24].
• To determine whether lipid raft association was essential for P2X1 receptor channel function we used the cholesterol-depleting agent methyl-beta-cyclodextrin (10 mm for 1 h) [24].
• This led to a redistribution of the P2X1 receptor throughout the sucrose gradient and reduced P2X1 receptor-mediated (alpha,beta-methylene ATP, 10 microm) currents in HEK293 cells by >90% and contractions of the rat tail artery by approximately 50% [24].

Other interactions of P2rx1

• Due to lack of any known antagonist for P2X4 it is unlikely that native P2X4 has previously been recognized as a P2X purinoceptor [22].
• Vanilloid receptor like 1 (VRL1) immunoreactivity in mammalian retina: colocalization with somatostatin and purinergic P2X1 receptors [23].
• No changes in P2X1 or P2X2 receptor expression were seen during the oestrous cycle [25].
• Of the P2 receptor subtypes examined, P2X1, P2X2 and P2Y1 receptors were found in the smooth muscle layer of intrarenal vessels [26].
• Immunocytochemistry showed strong P2X4 receptor expression partly associated with the membrane, weak P2X7 staining that was not associated with the cell membrane, and no P2X1 receptor immunoreactivity [27].

Analytical, diagnostic and therapeutic context of P2rx1

• Reverse transcription-polymerase chain reaction (RT-PCR) was used to characterize the expression of P2X receptor subunits (P2X1-P2X7) in different inner ear tissues [28].
• In this study we have used discontinuous sucrose density gradients, Western blot analysis, and cholesterol measurements to show that recombinant and smooth muscle (rat tail artery, vas deferens, and bladder) P2X1 receptors are present in cholesterol-rich lipid rafts and co-localize with the lipid raft markers flotillin-1 and -2 [24].
• Molecular cloning and functional expression of a novel rat heart P2X purinoceptor [29].
• The distribution of purinergic (P2X1 and P2X2) receptors on smooth muscle cells in relation to autonomic nerve varicosities in rat blood vessels has been determined using immunofluorescence and confocal microscopy [30].
• These findings are in broad agreement with earlier Northern blot studies on the PC12 P2X purinoceptor mRNA but differ from those for the vas deferens P2X purinoceptor mRNA, which had not previously been detected in adult brain [31].

References