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Neuroanatomical distribution and function of the vasopressin V-1B receptor in the rat brain deciphered using specific fluorescent ligands

Corbani, M. and Marir, R. and Truebai, M. and Chafai, M. and Vincent, A. and Tömböly, Csaba (2018) Neuroanatomical distribution and function of the vasopressin V-1B receptor in the rat brain deciphered using specific fluorescent ligands. GENERAL AND COMPARATIVE ENDOCRINOLOGY, 258. pp. 15-32. ISSN 0016-6480

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Abstract

It is now accepted that vasopressin, through V-1A/V-1B receptors, centrally regulates cognitive functions such as memory, affiliation, stress, fear and depression. However, the respective roles of these receptor isoforms and their contribution to stress-related pathologies remain uncertain. The development of new therapeutic treatments requires a precise knowledge of the distribution of these receptors within the brain, which has been so far hampered by the lack of selective V-1B markers. In the present study, we have determined the pharmacological properties of three new potent rat V-1B fluorescent ligands and demonstrated that they constitute valuable tools for simultaneous visualization and activation of native V-1B receptors in living rat brain tissue. Thus, d[Leu(4),Lys-Alexa 647)(8)]VP (analogue 3), the compound with the best affinity-selectivity/fluorescence ratio for the V-1B receptor emerged as the most promising. The rat brain regions most concerned by stress such as hippocampus, olfactory bulbs, cortex and amygdala display the highest V-1B fluorescent labelling with analogue 3. In the hippocampus CA(2), V-1B receptors are located on glutamatergic, not GABAergic neurones, and are absent from astrocytes. Using AVP-EGFP rats, we demonstrate the presence of V-1B autoreceptors on AVP-secreting neurones not only in the hypothalamus, but also sparsely in the hippocampus. Finally, using both electrophysiology and visualization of ERK phosphorylation, we show analogue 3-induced activation of the V-1B receptor in situ. This will help to analyse expression and functionality of V-1B receptors in the brain and contribute to further explore the AVPergic circuitry in normal and pathological conditions. (C) 2017 Elsevier Inc. All rights reserved.

Item Type: Article
Subjects: R Medicine / orvostudomány > RC Internal medicine / belgyógyászat
SWORD Depositor: MTMT SWORD
Depositing User: MTMT SWORD
Date Deposited: 30 Jan 2019 13:15
Last Modified: 30 Jan 2019 13:15
URI: http://real.mtak.hu/id/eprint/90760

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