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The Journal of Neuroscience, January 15, 1999, 19(2):737-746
ATP Stimulates Sympathetic Transmitter Release via Presynaptic
P2X Purinoceptors
Stefan
Boehm
Department of Neuropharmacology, University of Vienna, A-1090
Vienna, Austria
ATP is a fast transmitter in sympathetic ganglia and at the
sympathoeffector junction. In primary cultures of dissociated rat
superior cervical ganglion neurons, ATP elicits noradrenaline release
in an entirely Ca2+-dependent manner. Nevertheless,
ATP-evoked noradrenaline release was only partially reduced (by
~50%) when either Na+ or Ca2+
channels were blocked, which indicates that ATP receptors themselves mediated transmembrane Ca2+ entry. An "axonal"
preparation was obtained by removing ganglia from explant cultures,
which left a network of neurites behind; immunostaining for axonal and
dendritic markers revealed that all of these neurites were axons. In
this preparation, ATP raised intraaxonal Ca2+ and
triggered noradrenaline release, and these actions were not altered
when Ca2+ channels were blocked by
Cd2+. Hence, Ca2+-permeable
ATP-gated ion channels, i.e., P2X purinoceptors, are located at
presynaptic sites and directly mediate
Ca2+-dependent transmitter release. These
presynaptic P2X receptors displayed a rank order of agonist potency of
ATP 2-methylthio-ATP > ATP S
, -methylene-ATP , -methylene-L-ATP and
were blocked by suramin or PPADS. ATP, 2-methylthio-ATP, and ATP S
also evoked inward currents measured at neuronal somata, but there
these agonists were equipotent. Hence, presynaptic P2X receptors
resemble the cloned P2X2 subtype, but they appear to differ from
somatodendritic P2X receptors in terms of agonist sensitivity. Suramin
reduced depolarization-evoked noradrenaline release by up to 20%, when autoinhibitory mechanisms were inactivated by pertussis toxin. These
results indicate that presynaptic P2X purinoceptors mediate a positive,
whereas G-protein-coupled P2Y purinoceptors mediate a negative,
feedback modulation of sympathetic transmitter release.
Key words:
rat superior cervical ganglion neurons; noradrenaline
release; ATP; P2X receptors; presynaptic modulation; intracellular
Ca2+
Copyright © 1999 Society for Neuroscience 0270-6474/99/192737-10$05.00/0
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