Poster
# 110
Poster |
|
6th Internet World Congress for Biomedical Sciences |
Trevor Sharp(1), Elena Castro(2)
(1)Department of Clinical Pharmacology. University of Oxford - Oxford. United Kingdom
(2) Clinical Pharmacology. University of Oxford - Oxford. United Kingdom
|
 |
|
|
[Pharmacology] |
[Psychiatry] |
Scatchard and nonlinear regression analysis revealed that [3H]WAY-100635 interacted with a single class of binding sites in rat brain. This binding was saturable, specific and of high affinity in DRN (KD= 1.5 nM) and all the areas of the hippocampus tested, specifically CA1, CA3 and dentate gyrus (KD= 1.65-1.71 nM). The total number of binding sites in the DRN were of the same order of those in the hippocampal areas Table 1. At the concentration of [3H]WAY-100635 used in inhibition assays (3 nM) non-specific binding, as defined by 10 µM 5-HT, represented less than 10% of the total binding (data not shown).
(±)-Pindolol caused a concentration-dependent inhibition of [3H]WAY-100635 in all rat brain areas tested and the competition curves were best described by a single binding site with Hill coefficients close to unity.
Autoradiograms illustrating the inhibition by (±)-pindolol of [3H]WAY-100635 binding in the rat DRN and hippocampus are shown in figure 1. (±)-Pindolol did not discriminate between pre- and postsynaptic 5-HT1A binding sites. Thus, the inhibition curves for (±)-pindolol obtained from CA1, CA3 and dentate gyrus of the rat hippocampus produced Ki values (7.9- 8.7 nM) were not statistically different from the Ki value of the DRN (6.5 nM) (Table 2).
Human brain sections incubated with [3H]WAY-100635 revealed substantial 5-HT1A receptor binding in the DRN and CA1 of the hippocampus, with considerably weaker binding in CA3 and dentate gyrus. Due to the relatively weak signal observed in these later two regions, inhibition experiments were quantified only within CA1.
As with the rat, (±)-pindolol, demonstrated high affinity for the 5-HT1A binding sites in human hippocampus and DRN figure 2, and the competition curves for (±)-pindolol were best described by a single binding site. In contrast to the rat, (±)-pindolol showed a small degree of selectivity for the pre- versus postsynaptic 5-HT1A binding sites in the human. Thus, the Ki value of (±)-pindolol for the human DRN (8.9 nM) was lower than that for the CA1 of hippocampus (14.4 nM) and this difference was statistically significant (Table 2).
|
|
|
|
|
|
[Pharmacology] |
[Psychiatry] |
