The Journal of Neuroscience, August 15, 2001, 21(16):6308-6320
Adenosine A1 Receptors Reduce Release from Excitatory But Not
Inhibitory Synaptic Inputs onto Lateral Horn Neurons
Susan A.
Deuchars,
Ruth E.
Brooke, and
Jim
Deuchars
School of Biomedical Sciences, University of Leeds, Leeds, LS2 9NQ,
United Kingdom
Although adenosine is an important neuromodulator in the
CNS, its role in modulating sympathetic outflow at the level of
the spinal cord has not been studied. Because very little is known about adenosine A1 receptors (A1Rs) in the spinal cord, we
determined their location and role with particular reference to the
control of sympathetic preganglionic activity and interneuronal
activity in the rat. High levels of immunoreactivity for A1Rs were
observed throughout the spinal cord. Immunostaining was dense in the
intermediolateral cell column (IML) and intercalated nucleus, regions
containing retrogradely labeled sympathetic preganglionic neurons
(SPNs). Electron microscopy revealed A1R immunoreactivity (A1R-IR)
within presynaptic terminals and (to a lesser extent) postsynaptic
structures in the IML, as well as the luminal membrane of endothelial
cells lining capillaries. Using double-labeling techniques, some
presynaptic terminals were observed to synapse onto SPNs. To
investigate the effects of activating these A1Rs, visualized whole-cell
patch-clamp recordings were made from electrophysiologically and
morphologically identified SPNs and interneurons. Applications of the
A1R agonist cyclopentyladenosine (CPA) reduced the amplitude of
EPSPs elicited by stimulation of the lateral funiculus, an effect
blocked by the A1R antagonist 8-cyclopentyl-1,3-dipropylxanthine. These
effects were attributable to adenosine acting at a presynaptic
site because CPA application increased the paired-pulse ratio. CPA did
not affect evoked IPSPs. These data show that activating A1Rs reduces fast excitatory, but not inhibitory, transmission onto SPNs and interneurons in the IML and that A1Rs may play a protective role on neurons involved in the control of sympathetic outflow.
Key words:
sympathetic; adenosine A1 receptors; blood vessel; excitatory amino acid transmission; spinal cord; electron
microscopy
Copyright © 2001 Society for Neuroscience 0270-6474/01/21166308-13$05.00/0
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