EurekaMag
+ Translate
+ Most Popular
The pigeon tick (Argas reflexus): its biology, ecology, and epidemiological aspects
Prevalence of hemoglobin abnormalities in Kebili (Tunisian South)
Lipogranuloma: a preventable complication of dacryocystorhinostomy
Value of basal plasma cortisol assays in the assessment of pituitary-adrenal insufficiency
Bees from the Belgian Congo. The acraensis group of Anthophora
Placing gingival retraction cord
Total serum IgE, allergy skin testing, and the radioallergosorbent test for the diagnosis of allergy in asthmatic children
Acariens plumicoles Analgesoidea parasites des oiseaux du Maroc
Injuries of terminal phalanges of the fingers in children
Biology of flowering and nectar production in pear (Pyrus communis)
Das Reliktvorkommen der Aspisviper (Vipera aspis L.) im Schwarzwald
Hydrological modelling of drained blanket peatland
Pathologic morphology and clinical significance of the anomalous origin of the left circumflex coronary artery from the right coronary artery. General review and autopsy analysis of 30 cases
Cyto genetic analyses of lymphocyte cultures after exposure to calcium cyclamate
Axelrodia riesei, a new characoid fish from Upper Rio Meta in Colombia With remarks concerning the genus Axelrodia and description of a similar, sympatric, Hyphessobrycon-species
Favorable evolution of a case of tuberculosis of pancreas under antibiotic action
RIFM fragrance ingredient safety assessment, Valencene, CAS Registry Number 4630-07-3
Parenteral microemulsions: an overview
Temperate pasture: management for grazing and conservation
Evaluation of a new coprocessed compound based on lactose and maize starch for tablet formulation
Thermal expansion and cracking of three confined water-saturated igneous rocks to 800C
Revision of the genera of the tribe Stigmoderini (Coleoptera: Buprestidae) a discussion of phylogenetic relationships
Anal tuberculosis. Report of a case
Gastric tuberculosis in the past and present
Adaptive responses of the cardiovascular system to prolonged spaceflight conditions: assessment with Holter monitoring

P2X receptor chimeras highlight roles of the amino terminus to partial agonist efficacy, the carboxyl terminus to recovery from desensitization, and independent regulation of channel transitions


P2X receptor chimeras highlight roles of the amino terminus to partial agonist efficacy, the carboxyl terminus to recovery from desensitization, and independent regulation of channel transitions



Journal of Biological Chemistry 288(29): 21412-21421



ISSN/ISBN: 0021-9258

PMID: 23740251

DOI: 10.1074/jbc.m113.464651

P2X receptor subtypes can be distinguished by their sensitivity to ATP analogues and selective antagonists. We have used chimeras between human P2X1 and P2X2 receptors to address the contribution of the extracellular ligand binding loop, transmembrane segments (TM1 and TM2), and intracellular amino and carboxyl termini to the action of partial agonists (higher potency and efficacy of BzATP and Ap5A at P2X1 receptors) and antagonists. Sensitivity to the antagonists NF449, suramin, and PPADS was conferred by the nature of the extracellular loop (e.g. nanomolar for NF449 at P2X1 and P2X2-1EXT and micromolar at P2X2 and P2X1-2EXT). In contrast, the effectiveness of partial agonists was similar to P2X1 levels for both of the loop transfers, suggesting that interactions with the rest of the receptor played an important role. Swapping TM2 had reciprocal effects on partial agonist efficacy. However, TM1 swaps increased partial agonist efficacy at both chimeras, and this was similar for swaps of both TM1 and 2. Changing the amino terminus had no effect on agonist potency but increased partial agonist efficacy at P2X2-1N and decreased it at P2X1-2N chimeras, demonstrating that potency and efficacy can be independently regulated. Chimeras and point mutations also identified residues in the carboxyl terminus that regulated recovery from channel desensitization. These results show that interactions among the intracellular, transmembrane, and extracellular portions of the receptor regulate channel properties and suggest that transitions to channel opening, the behavior of the open channel, and recovery from the desensitized state can be controlled independently.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 054831696

Download citation: RISBibTeXText

Related references

Acute agonist-mediated desensitization of the human a1a-adrenergic receptor is primarily independent of carboxyl terminus regulation. Implications for regulation of a1aAR splice variants. The Journal of Biological Chemistry 277(11): 70-9, 2002

Acute agonist-mediated desensitization of the human alpha 1a-adrenergic receptor is primarily independent of carboxyl terminus regulation: implications for regulation of alpha 1aAR splice variants. Journal of Biological Chemistry 277(11): 9570-9579, 2002

Truncation of the receptor carboxyl terminus impairs agonist-dependent phosphorylation and desensitization of the a1B-adrenergic receptor. The Journal of Biological Chemistry 269: 887-93, 1994

Truncation of the receptor carboxyl terminus impairs agonist-induced desensitization of the type-1A angiotensin II receptor. Hypertension 28(3): 530, 1996

The role of the D-1 receptor carboxyl terminus in desensitization and down-regulation. Society for Neuroscience Abstracts 22(1-3): 1315, 1996

Differential regulation of the uridine nucleotide-activated P2Y4 and P2Y6 receptors. Ser-333 and Ser-334 in the carboxyl terminus are involed in agonist-dependent phosphorylation desensitization and internalization of the P2Y4 receptor. Journal of Biological Chemistry 276(15): 11939-11948, 2001

Differential regulation of the uridine nucleotide-activated P2Y4 and P2Y6 receptors. SER-333 and SER-334 in the carboxyl terminus are involved in agonist-dependent phosphorylation desensitization and internalization of the P2Y4 receptor. Journal of Biological Chemistry 276(15): 11939-11948, 2000

Truncation of the receptor carboxyl terminus impairs agonist-dependent phosphorylation and desensitization of the alpha 1B-adrenergic receptor. Journal of Biological Chemistry 269(36): 22887-22893, 1994

The long cytoplasmic carboxyl terminus of the prostaglandin E2 receptor EP4 subtype is essential for agonist-induced desensitization. Molecular Pharmacology 51(2): 343-349, 1997

Phosphorylation of four amino acid residues in the carboxyl terminus of the rat somatostatin receptor subtype 3 is crucial for its desensitization and internalization. Journal of Biological Chemistry 272(38): 23769-23774, 1997

Role of carboxyl terminus of μ- and δ-opioid receptor in agonist -induced down-regulation. Molecular Brain Research 54(1): 24-34, 1998

Role of carboxyl terminus of mu-and delta-opioid receptor in agonist-induced down-regulation. Brain Research. Molecular Brain Research 54(1): 24-34, 1998

Chimeras that alter the amino or carboxyl terminus of the alpha subunit of g s a cyclic amp synthesis. Journal of Cellular Biochemistry Suppl (13 Part E): 252, 1989

Independent regulation of human-ERG K+ channel activation and deactivation gating by two different domains in the amino terminus. European Biophysics Journal 29(4-5): 343, 2000

Desensitization of the secretin receptor The role of phosphorylation of the carboxyl-terminus. Molecular Biology of the Cell 6(Suppl ): 56A, 1995