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Review
. 2004 Mar 1;555(Pt 2):311-21.
doi: 10.1113/jphysiol.2003.056697. Epub 2003 Dec 23.

Purinergic regulation of epithelial transport

R Elaine Bucheimer  1 , Joel Linden
Affiliations
Review

Purinergic regulation of epithelial transport

R Elaine Bucheimer et al. J Physiol. .

Abstract

Purinergic receptors are a family of ubiquitous transmembrane receptors comprising two classes, P1 and P2 receptors, which are activated by adenosine and extracellular nucleotides (i.e. ATP, ADP, UTP and UDP), respectively. These receptors play a significant role in regulating ion transport in epithelial tissues through a variety of intracellular signalling pathways. Activation of these receptors is partially dependent on ATP (or UTP) release from cells and its subsequent metabolism, and this release can be triggered by a number of stimuli, often in the setting of cellular damage. The function of P2Y receptor stimulation is primarily via signalling through the G(q)/PLC-beta pathway and subsequent activation of Ca(2+)-dependent ion channels. P1 signalling is complex, with each of the four P1 receptors A(1), A(2A), A(2B), and A(3) having a unique role in different epithelial tissue types. In colonic epithelium the A(2B) receptor plays a prominent role in regulating Cl(-) and water secretion. In airway epithelium, A(2B) and A(1) receptors are implicated in the control of Cl(-) and other currents. In the renal tubular epithelium, A(1), A(2A), and A(3) receptors have all been identified as playing a role in controlling the ionic composition of the lumenal fluid. Here we discuss the intracellular signalling pathways for each of these receptors in various epithelial tissues and their roles in pathophysiological conditions such as cystic fibrosis.

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Figures

Figure 1
Figure 1. Purinergic receptors important in regulating epithelial ion transport
The P1 receptors A2A and A2B classically signal through Gs, resulting in an increase in cAMP and activation of PKA. A rise in intracellular Ca2+ noted in some cells in response to A2B receptor activation may result from receptor coupling to Gq and activation of PLC-β or from cAMP-activation of Rap2B that raises intracellular Ca2+ via PLC-ɛ. This rise in intracellular Ca2+ by either of these mechanisms likely accounts for the activation of PLA2 that contributes to the A2B activated Cl− current. The A1 receptor has been shown to be active in airway epithelial cell lines and evokes a Ca2+ response through the βγ subunits of Gi. This triggers basolateral K+ efflux and may trigger Cl− release. P2X receptors are ligand-gated ion channels and increase cell permeability to Na+ or Ca2+. P2Y receptors classically signal through Gq, resulting in an increase in intracellular Ca2+ and activation of Ca2+-activated Cl− and K+ channels, although a Ca2+-independent Cl− current resulting from P2Y activation has been identified.
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References

    1. Abbracchio MP, Boeynaems JM, Barnard EA, Boyer JL, Kennedy C, Miras-Portugal MT, King BF, Gachet C, Jacobson KA, Weisman GA, Burnstock G. Characterization of the UDP-glucose receptor (re-named here the P2Y14 receptor) adds diversity to the P2Y receptor family. Trends Pharmacol Sci. 2003;24:52–55. - PMC - PubMed
    1. Anderson MP, Sheppard DN, Berger HA, Welsh MJ. Chloride channels in the apical membrane of normal and cystic fibrosis airway and intestinal epithelia. Am J Physiol. 1992;263:L1–L14. - PubMed
    1. Anderson MP, Welsh MJ. Calcium and cAMP activate different chloride channels in the apical membrane of normal and cystic fibrosis epithelia. Proc Natl Acad Sci U S A. 1991;88:6003–6007. - PMC - PubMed
    1. Arispe N, Ma J, Jacobson KA, Pollard HB. Direct activation of cystic fibrosis transmembrane conductance regulator channels by 8-cyclopentyl-1,3-dipropylxanthine (CPX) and 1,3-diallyl-8-cyclohexylxanthine (DAX) J Biol Chem. 1998;273:5727–5734. - PubMed
    1. Avila MY, Stone RA, Civan MM. A(1)-, A(2A)- and A(3)-subtype adenosine receptors modulate intraocular pressure in the mouse. Br J Pharmacol. 2001;134:241–245. - PMC - PubMed

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