Martins Sá, Renato W;
Theparambil, Shefeeq M;
Dos Santos, Karoline Martins;
Christie, Isabel N;
Marina, Nephtali;
Cardoso, Barbara V;
Hosford, Patrick S;
(2023)
Salt-loading promotes extracellular ATP release mediated by glial cells in the hypothalamic paraventricular nucleus of rats.
Molecular and Cellular Neuroscience
, 124
, Article 103806. 10.1016/j.mcn.2022.103806.
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Abstract
Previously, we have shown that purinergic signalling is involved in the control of hyperosmotic-induced sympathoexcitation at the level of the PVN, via activation of P2X receptors. However, the source(s) of ATP that drives osmotically-induced increases in sympathetic outflow remained undetermined. Here, we tested the two competing hypotheses that either (1) higher extracellular ATP in PVN during salt loading (SL) is a result of a failure of ectonucleotidases to metabolize ATP; and/or (2) SL can stimulate PVN astrocytes to release ATP. Rats were salt loaded with a 2 % NaCl solution replacing drinking water up to 4 days, an experimental model known to cause a gradual increase in blood pressure and plasma osmolarity. Immunohistochemical assessment of glial-fibrillary acidic protein (GFAP) revealed increased glial cell reactivity in the PVN of rats after 4 days of high salt exposure. ATP and adenosine release measurements via biosensors in hypothalamic slices showed that baseline ATP release was increased 17-fold in the PVN while adenosine remained unchanged. Disruption of Ca2+-dependent vesicular release mechanisms in PVN astrocytes by virally-driven expression of a dominant-negative SNARE protein decreased the release of ATP. The activity of ectonucleotidases quantified in vitro by production of adenosine from ATP was increased in SL group. Our results showed that SL stimulates the release of ATP in the PVN, at least in part, from glial cells by a vesicle-mediated route and likely contributes to the neural control of circulation during osmotic challenges.
| Type: | Article |
|---|---|
| Title: | Salt-loading promotes extracellular ATP release mediated by glial cells in the hypothalamic paraventricular nucleus of rats |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.mcn.2022.103806 |
| Publisher version: | https://doi.org/10.1016/j.mcn.2022.103806 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Adenosine, Astrocytes, ATP, Hypothalamus, Salt-loading |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10163033 |
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