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Cell Mol Neurobiol. 1997 Aug;17(4):401-15.

Beta-adrenoceptors in the tree shrew brain. I. Distribution and characterization of [125I]iodocyanopindolol binding sites.

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1
German Primate Center, Göttingen, Germany.

Abstract

1. The number and distribution pattern of beta-adrenergic receptors in the brain have been reported to be species specific. The aim of the present study was to describe binding of the beta-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 beta 1- and beta 2-adrenoceptors, serotonin binding sites had to be blocked by 100 microM 5HT. 3. Binding of the radioligand to beta 1- and beta 2-adrenoceptors was characterized using the beta 1-specific antagonist CGP20712A and the beta 2-specific antagonist ICI118.551. beta 1-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 Ki values for CGP20712A, showing that various affinity states of beta 1-adrenoceptors are present in the brain (Ki: 0.61 nM to 67.1 microM). In the hippocampus, only low-affinity beta 1-adrenoceptors were detected (Ki: 1.3 +/- 0.2 microM). Since it is known that 125ICYP labels not only membrane bound but also internalized beta-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 beta 2-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 beta-adrenoceptors, high- and low-affinity binding sites for the beta 2-selective antagonist ICI118.551 were observed, indicating that 125ICYP labels membrane bound and internalized beta 2-adrenoceptors. Only in the cerebellar molecular layer was a high percentage of high-affinity beta 2-adrenoceptors detected (Ki for ICI118.551 was 1.8 +/- 0.3 nM for 90% of the receptors). 6. In conclusion, beta 1- and beta 2-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 beta-adrenoceptor system in male tree shrews are described in the following paper.

PMID:
9262867
[Indexed for MEDLINE]

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