ISSN:
1573-6830
Keywords:
β-adrenoceptor
;
125I-cyanopindolol
;
sequestration
;
down-regulation
;
CGP20712A
;
ICI118.551
Source:
Springer Online Journal Archives 1860-2000
Topics:
Biology
Notes:
Abstract 1. The number and distribution pattern of β-adrenergic receptors in the brain have been reported to be species specific. The aim of the present study was to describe binding of the β-adrenoceptor ligand [125I]iodocyanopindolol in the brain of the tree shrew (Tupaia belangeri), a species which provides an appropriate model for studies of psychosocial stress and its consequences on central nervous processes. 2. 125I-Iodocyanopindolol (125ICYP) labeling revealed a high degree of nonspecific binding, which was due mainly to interactions of this ligand with serotonin binding sites. For a quantitative evaluation of β1- and β2-adrenoceptors, serotonin binding sites had to be blocked by 100 μM 5HT. 3. Binding of the radioligand to β1- and β2-adrenoceptors was characterized using the β1-specific antagonist CGP20712A and the β2-specific antagonist ICI118.551. β1-adrenoceptor binding is present in the whole brain, revealing low receptor numbers in most brain regions (up to 1.5 to 2.7 fmol/mg). A slight enrichment was observed in cortical areas (lateral orbital cortex: 4.0±0.7 fmol/mg) and in the cerebellar molecular layer (8.7±1.0 fmol/mg). 4. Competition experiments demonstrated high- and low-affinity binding sites with considerable variations in K i values for CGP20712A, showing that various affinity states of β1-adrenoceptors are present in the brain (K i: 0.61 nM to 67.1 μM). In the hippocampus, only low-affinity β1-adrenoceptors were detected (K i: 1.3±0.2 μM). Since it is known that 125ICYP labels not only membrane bound but also internalized β-adrenoceptors, it can be assumed that the large population of the low-affinity sites represents internalized receptors which may be abundant due to a high sequestration rate. 5. High numbers of β2-adrenoceptors are present in only a few brain structures of tree shrews (external layer of the olfactory bulb, 15.8±2.0 fmol/mg; claustrum, 19.3±1.5 fmol/mg; anteroventral thalamic nucleus, 19.4±1.5 fmol/mg; cerebellar molecular layer, 55.0±4.3 fmol/mg). Also for this class of β-adrenoceptors, high- and low-affinity binding sites for the β2-selective antagonist ICI118.551 were observed, indicating that 125ICYP labels membrane bound and internalized β2-adrenoceptors. Only in the cerebellar molecular layer was a high percentage of high-affinity β2-adrenoceptors detected (K i for ICI118.551 was 1.8±0.3 nM for 90% of the receptors). 6. In conclusion, β1- and β2-adrenoceptor binding can be localized and quantified by in vitro receptor autoradiography in the brains of tree shrews when serotonergic binding sites are blocked. Modulatory effects of long-term psychosocial conflict on the central nervous β-adrenoceptor system in male tree shrews are described in the following paper.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1026335327150
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