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Citation
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HERO ID
7671023
Reference Type
Journal Article
Title
Subcellular localization of adenosine A(1) receptors in nerve terminals and synapses of the rat hippocampus
Author(s)
Rebola, N; Pinheiro, PC; Oliveira, CR; Malva, JO; Cunha, RA
Year
2003
Is Peer Reviewed?
Yes
Journal
Brain Research
ISSN:
0006-8993
EISSN:
1872-6240
Publisher
Elsevier
Location
AMSTERDAM
Volume
987
Issue
1
Page Numbers
49-58
Language
English
PMID
14499945
DOI
10.1016/s0006-8993(03)03247-5
Web of Science Id
WOS:000185945800007
Abstract
Adenosine is a neuromodulator in the CNS that mainly acts through pre- and postsynaptic A(1) receptors to inhibit the release of excitatory neurotransmitters and NMDA receptor function. This might result from a highly localized distribution of A(1) receptors in the active zone and postsynaptic density of CNS synapses that we now investigated in the rat hippocampus. The binding density of the selective A(1) receptor antagonist, [3H]1,3-dipropyl-8-cyclopentylxanthine ([3H]DPCPX), was enriched in membranes from Percoll-purified nerve terminals (B(max)=1839+/-52 fM/mg protein) compared to total membranes from the hippocampus (B(max)=984+/-31 fM/mg protein), the same occurring with A(1) receptor immunoreactivity. [3H]DPCPX binding occurred mainly to the plasma membrane rather than to intracellular sites, since the binding of the membrane permeable A(1) receptor ligand [3H]DPCPX to intact hippocampal nerve terminals (B(max)=1901+/-192 fM/mg protein) was markedly reduced (B(max)=321+/-30 fM/mg protein) by the membrane impermeable adenosine receptor antagonist, 8-sulfophenyltheophilline (25 microM). Further subcellular fractionation of hippocampal nerve terminals revealed that A(1) receptor immunoreactivity was strategically located in the active zone of presynaptic nerve terminals, as expected to understand the efficiency of A(1) receptors to depress neurotransmitter release. A(1) Receptors were also present in nerve terminals outside the active zone in accordance with the existence of a presynaptic A(1) receptor reserve. Finally, A(1) receptor immunoreactivity was evident in the postsynaptic density together with NMDA receptor subunits 1, 2A and 2B and with N-and P/Q-type calcium channel immunoreactivity, emphasizing the importance of A(1) receptors in the control of dendritic integration.
Keywords
A1 receptor; Active zone; Adenosine; Calcium channel; Hippocampus; Nerve terminal; NMDA receptor; Postsynaptic density; Synaptosome
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