Neuroscience 2002 Abstract
| Presentation Number: | 515.2 |
|---|---|
| Abstract Title: | Evidence that CGS 21680 binding to non-striatal regions of mouse brain requires A<sub>1</sub> receptors. |
| Authors: |
Lopes, L. V.*1
; Halldner-Henriksson, L.3
; Rebola, N.2
; Cunha, R. A.2
; Fredholm, B. B.3
1Lab Neurosci, Fac Med Lisbon, Lisbon, Portugal 2Ctr Neurosci Coimbra, Inst. Biochem, Fac Med Coimbra, Coimbra, Portugal 3Dept Physiol and Pharmacol, Karolinska Institutet, Stockholm, Sweden |
| Primary Theme and Topics |
Synaptic Transmission and Excitability - G-Protein Linked Receptors -- Purine receptors |
| Session: |
515. G-protein linked receptors: mechanisms Slide |
| Presentation Time: | Tuesday, November 5, 2002 1:15 PM-1:30 PM |
| Location: | Room 203A |
| Keywords: | ADENOSINE A2A RECEPTORS, KNOCKOUT, HIPPOCAMPUS, CORTEX |
Autoradiographic studies in adenosine A 1 and A 2A receptor knockout (KO) mice (Johansson et al, 2001, PNAS, 98, 9407; Ledent et al., 1997, Nature, 388, 624) indicated that the binding of the purportedly A 2A receptor selective agonist CGS21680 in the hippocampus is not only to an A 2A receptor, but requires the presence of A 1 receptors (Fredholm et al, 2001, SFN proceeds.). We now confirmed and extended these observations. Saturation binding curves were performed using the selective A 1 antagonist, [3H]DPCPX and the A 2A agonist[3H]CGS21680 in membranes from different mice brain regions. The A 1-KO mice displayed a non detectable binding of [3H]DPCPX(0.1-10 nM) in the hippocampus, striatum and cortex, in contrast to wild type mice (WT) which displayed Bmax values ranging from 4196(3497-4896) to 1747(1399-2095) fmol/mg protein. However, in A 1-KO mice, we observed no detectable binding of [3H]CGS21680(0.1 to 20 nM) to the hippocampus and a lower binding in the cortex. Also, [3H]CGS21680 binding in the hippocampus of A 2A -KO mice was unaltered if compared to the WT. In the striatum, CGS21680 binding disappeared in A 2A -KO mice and was unaltered in A 1-KO mice. In parallel, Western blots in rat cortical nerve terminals showed A 2A receptor signals and A 2A immunoreactivity was found in cortical neurons in culture. These preliminary data confirm that, although A 2A receptors exist in cortical neurons, much of CGS21680 binding to hippocampus and cortex is to a non-A 2A receptor site that is dependent on the presence of A 1 receptors.
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2002 Neuroscience Meeting Planner. Orlando, FL: Society for Neuroscience, 2002. Online.
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