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Physiological Reviews, Vol. 82, No. 4, October 2002, pp. 1013-1067; 10.1152/physrev.00015.2002.
Copyright ©2002 by the American Physiological Society
Institute of Molecular Physiology, University of Sheffield, Western Bank, Sheffield, United Kingdom
North, R. Alan
Molecular Physiology of P2X Receptors. Physiol. Rev. 82: 1013-1067, 2002.
P2X receptors are membrane ion
channels that open in response to the binding of extracellular ATP.
Seven genes in vertebrates encode P2X receptor subunits, which
are 40-50% identical in amino acid sequence. Each subunit has two
transmembrane domains, separated by an extracellular domain (~280
amino acids). Channels form as multimers of several subunits. Homomeric
P2X1, P2X2, P2X3, P2X4, P2X5, and P2X7 channels and heteromeric
P2X2/3 and P2X1/5 channels have been most fully
characterized following heterologous expression. Some agonists (e.g.,
-methylene ATP) and antagonists [e.g., 2',3'-O-(2,4,6-trinitrophenyl)-ATP] are strongly selective
for receptors containing P2X1 and P2X3
subunits. All P2X receptors are permeable to small monovalent cations;
some have significant calcium or anion permeability. In many cells,
activation of homomeric P2X7 receptors induces a
permeability increase to larger organic cations including some
fluorescent dyes and also signals to the cytoskeleton; these changes
probably involve additional interacting proteins. P2X receptors are
abundantly distributed, and functional responses are seen in neurons,
glia, epithelia, endothelia, bone, muscle, and hemopoietic tissues. The
molecular composition of native receptors is becoming understood, and
some cells express more than one type of P2X receptor. On smooth
muscles, P2X receptors respond to ATP released from sympathetic motor
nerves (e.g., in ejaculation). On sensory nerves, they are involved in
the initiation of afferent signals in several viscera (e.g., bladder,
intestine) and play a key role in sensing tissue-damaging and
inflammatory stimuli. Paracrine roles for ATP signaling through P2X
receptors are likely in neurohypophysis, ducted glands, airway
epithelia, kidney, bone, and hemopoietic tissues. In the last case,
P2X7 receptor activation stimulates cytokine release by
engaging intracellular signaling pathways.
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