Activation of adenosine A2A receptors alters postsynaptic currents and depolarizes neurons of the supraoptic nucleus

American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Todd A PonzioGlenn I Hatton

Abstract

Supraoptic nucleus (SON) neurons secrete oxytocin or vasopressin in response to various physiological stimuli (e.g., lactation/suckling, dehydration). Released near fenestrated capillaries of the neurohypophysis, these peptides enter the blood and travel to peripheral target organs. The pervasive neuromodulator adenosine, acting at A1 receptors, is an important inhibitory regulator of magnocellular neuroendocrine cell activity. Another high-affinity adenosine receptor exists in this system, however. We examined the physiological effects of adenosine A2A receptor activation and determined its localization among various cell types within the SON. In whole cell patch-clamp recordings from rat brain slices, application of the selective adenosine A2A receptor agonist CGS-21680 caused membrane depolarizations in SON neurons, often leading to increased firing activity. Membrane potential changes were persistent (>10 min) and could be blocked by the selective A2A receptor antagonist ZM-241385, or GDP-beta-S, the latter suggesting postsynaptic sites of action. However, +/--alpha-methyl-(4-carboxyphenyl)glycine or TTX also blocked CGS-21680 effects, indicating secondary actions on postsynaptic neurons. In voltage-clamp mode, application ...Continue Reading

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Citations

Jul 2, 2016·Journal of Neurochemistry·Rodrigo A Cunha
Oct 28, 2017·Nature Reviews. Endocrinology·Jerome Clasadonte, Vincent Prevot
Mar 8, 2018·Journal of Neuroendocrinology·José R LemosSonia Ortiz-Miranda
May 15, 2020·Journal of Neuroendocrinology·Colin H BrownJavier E Stern

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