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Modification of adenosine A1 and A2A receptor density in the hippocampus of streptozotocin-induced diabetic rats

Duarte, João M N LU orcid ; Oliveira, Catarina R ; Ambrósio, António F and Cunha, Rodrigo A (2006) In Neurochemistry International 48(2). p.144-150
Abstract

Adenosine A(1) and A(2A) receptors are neuromodulatory systems that can control mnemonic behavior, which is modified by diabetes. Since the density of these adenosine receptors can change upon chronic noxious brain conditions, we now tested if the density of A(1) and A(2A) receptors was modified in the hippocampus of streptozotocin-induced diabetic rats. The binding density of the selective A(1) receptor antagonist, (3)H-DPCPX, was decreased by 36% in total hippocampal membranes 7 days after induction of diabetes and this down-regulation was maintained after 30 and 90 days, which was also confirmed by Western blot analysis of A(1) receptor immunoreactivity. In contrast, the binding density of the selective A(2A) receptor antagonist,... (More)

Adenosine A(1) and A(2A) receptors are neuromodulatory systems that can control mnemonic behavior, which is modified by diabetes. Since the density of these adenosine receptors can change upon chronic noxious brain conditions, we now tested if the density of A(1) and A(2A) receptors was modified in the hippocampus of streptozotocin-induced diabetic rats. The binding density of the selective A(1) receptor antagonist, (3)H-DPCPX, was decreased by 36% in total hippocampal membranes 7 days after induction of diabetes and this down-regulation was maintained after 30 and 90 days, which was also confirmed by Western blot analysis of A(1) receptor immunoreactivity. In contrast, the binding density of the selective A(2A) receptor antagonist, (3)H-SCH 58261, was enhanced by 83% in total hippocampal membranes 7 days after induction of diabetes and this up-regulation persisted after 30 and 90 days. These results show that the balance between inhibitory A(1) and facilitatory A(2A) adenosine receptors is modified in the hippocampus of streptozotocin-induced diabetic rats. Thus, the most abundant A(1) receptors are down-regulated and there is an up-regulation of A(2A) receptors, suggesting a gain of function of hippocampal A(2A) receptors compared to A(1) receptors in diabetes, as has been observed in other chronic noxious brain conditions where A(2A) receptor blockade affords robust neuroprotection.

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author
; ; and
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Animals, Blotting, Western, Diabetes Mellitus, Experimental/metabolism, Hippocampus/metabolism, Male, Rats, Rats, Wistar, Receptor, Adenosine A1/metabolism, Receptor, Adenosine A2A/metabolism, Streptozocin
in
Neurochemistry International
volume
48
issue
2
pages
7 pages
publisher
Elsevier
external identifiers
  • pmid:16256246
  • scopus:29244450466
ISSN
0197-0186
DOI
10.1016/j.neuint.2005.08.008
language
English
LU publication?
no
id
96450d92-0fbf-4060-81b4-e00294f53002
date added to LUP
2019-02-22 09:19:36
date last changed
2024-01-30 12:19:11
@article{96450d92-0fbf-4060-81b4-e00294f53002,
  abstract     = {{<p>Adenosine A(1) and A(2A) receptors are neuromodulatory systems that can control mnemonic behavior, which is modified by diabetes. Since the density of these adenosine receptors can change upon chronic noxious brain conditions, we now tested if the density of A(1) and A(2A) receptors was modified in the hippocampus of streptozotocin-induced diabetic rats. The binding density of the selective A(1) receptor antagonist, (3)H-DPCPX, was decreased by 36% in total hippocampal membranes 7 days after induction of diabetes and this down-regulation was maintained after 30 and 90 days, which was also confirmed by Western blot analysis of A(1) receptor immunoreactivity. In contrast, the binding density of the selective A(2A) receptor antagonist, (3)H-SCH 58261, was enhanced by 83% in total hippocampal membranes 7 days after induction of diabetes and this up-regulation persisted after 30 and 90 days. These results show that the balance between inhibitory A(1) and facilitatory A(2A) adenosine receptors is modified in the hippocampus of streptozotocin-induced diabetic rats. Thus, the most abundant A(1) receptors are down-regulated and there is an up-regulation of A(2A) receptors, suggesting a gain of function of hippocampal A(2A) receptors compared to A(1) receptors in diabetes, as has been observed in other chronic noxious brain conditions where A(2A) receptor blockade affords robust neuroprotection.</p>}},
  author       = {{Duarte, João M N and Oliveira, Catarina R and Ambrósio, António F and Cunha, Rodrigo A}},
  issn         = {{0197-0186}},
  keywords     = {{Animals; Blotting, Western; Diabetes Mellitus, Experimental/metabolism; Hippocampus/metabolism; Male; Rats; Rats, Wistar; Receptor, Adenosine A1/metabolism; Receptor, Adenosine A2A/metabolism; Streptozocin}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{144--150}},
  publisher    = {{Elsevier}},
  series       = {{Neurochemistry International}},
  title        = {{Modification of adenosine A1 and A2A receptor density in the hippocampus of streptozotocin-induced diabetic rats}},
  url          = {{http://dx.doi.org/10.1016/j.neuint.2005.08.008}},
  doi          = {{10.1016/j.neuint.2005.08.008}},
  volume       = {{48}},
  year         = {{2006}},
}