HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 40, 41650-41657, October 1, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/40/41650    most recent M408203200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Agboh, Kelvin. C. Articles by Ennion, S. J. Search for Related Content PubMed PubMed Citation Articles by Agboh, Kelvin. C. Articles by Ennion, S. J. Social Bookmarking                      What's this?

Functional Characterization of a P2X Receptor from Schistosoma mansoni^*

Kelvin. C. Agboh, Tania E. Webb, Richard J. Evans, and Steven J. Ennion¶

From the Department of Cell Physiology and Pharmacology, University of Leicester, P. O. Box 138, Leicester LE1 9HN, United Kingdom and the Cell Signalling Laboratory, Leicester School of Pharmacy, The Hawthorn Building, De Montfort University, Leicester LE1 9BH, United Kingdom

The cloning and characterization of a P2X receptor (schP2X) from the parasitic blood fluke Schistosoma mansoni provides the first example of a non-vertebrate ATP-gated ion channel. A number of functionally important amino acid residues conserved throughout vertebrate P2X receptors, including 10 extracellular cysteines, aromatic and positively charged residues involved in ATP recognition, and a consensus protein kinase C site in the amino-terminal tail, are also present in schP2X. Overall, the amino acid sequence identity of schP2X with human P2X_1–7 receptors ranges from 25.8 to 36.6%. ATP evoked concentration-dependent currents at schP2X channels expressed in Xenopus oocytes with an EC₅₀ of 22.1 µM. 2',3'-O-(4-Benzoylbenzoyl)adenosine 5'-triphosphate (Bz-ATP) was a partial agonist (maximum response 75.4 ± 4.4% that of ATP) with a higher potency (EC₅₀ of 3.6 µM) than ATP. Suramin and pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid blocked schP2X responses to 100 µM ATP with IC₅₀ values of 9.6 and 0.5 µM, respectively. Ivermectin (10 µM) potentiated currents to both ATP and Bz-ATP by 60% with a minimal effect on potency (EC₅₀ of 18.2 and 1.6 µM, respectively). The relative permeability of schP2X expressed in HEK293 cells to various cations was determined under bi-ionic conditions. schP2X has a relatively high calcium permeability (P_Ca/P_Na = 3.80 ± 0.29) and an estimated minimum pore diameter similar to that of vertebrate P2X receptors. SchP2X provides a useful comparative model for the better understanding of human P2X receptor function and may also provide an alternative drug target for treatment of schistosomiasis.

Received for publication, July 20, 2004

^* This work was supported by a project grant from the Biotechnology and Biological Sciences Research Council (BBSRC) (to S. J. E), a BBSRC Co-operative Awards in Science and Engineering (CASE) studentship (to K. C. A.), and a Wellcome trust program grant (to R. J. E.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank^TM/EBI Data Bank with accession number(s) AJ783803.

^¶ To whom correspondence should be addressed. Tel.: 44-0116-252-3081; Fax: 44-0116-252-5045; E-mail: se15{at}le.ac.uk.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				G. Burnstock Unresolved issues and controversies in purinergic signalling J. Physiol., July 15, 2008; 586(14): 3307 - 3312. [Abstract] [Full Text] [PDF]

				S. J. Fountain, L. Cao, M. T. Young, and R. A. North Permeation Properties of a P2X Receptor in the Green Algae Ostreococcus tauri J. Biol. Chem., May 30, 2008; 283(22): 15122 - 15126. [Abstract] [Full Text] [PDF]

				G. Burnstock Physiology and Pathophysiology of Purinergic Neurotransmission Physiol Rev, April 1, 2007; 87(2): 659 - 797. [Abstract] [Full Text] [PDF]

				W. J. Wilkinson, L.-H. Jiang, A. Surprenant, and R. A. North Role of Ectodomain Lysines in the Subunits of the Heteromeric P2X2/3 Receptor Mol. Pharmacol., October 1, 2006; 70(4): 1159 - 1163. [Abstract] [Full Text] [PDF]

				T. Nakano, H. Inoue, S. Fukuyama, K. Matsumoto, M. Matsumura, M. Tsuda, T. Matsumoto, H. Aizawa, and Y. Nakanishi Niflumic Acid Suppresses Interleukin-13-induced Asthma Phenotypes Am. J. Respir. Crit. Care Med., June 1, 2006; 173(11): 1216 - 1221. [Abstract] [Full Text] [PDF]

				G. Burnstock Pathophysiology and therapeutic potential of purinergic signaling. Pharmacol. Rev., March 1, 2006; 58(1): 58 - 86. [Abstract] [Full Text] [PDF]