Purinergic and glutamatergic interactions in the hypothalamic paraventricular nucleus modulate sympathetic outflow

Ferreira‐Neto, Hildebrando Candido; Yao, Song T.; Antunes, Vagner Roberto

doi:10.1007/s11302-013-9352-9

Cited by 12 publications

(18 citation statements)

References 60 publications

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“…Our results demonstrate that exogenous ATP increases the firing activity of PVN sympathetic neurons, an effect that was dependent on P2 receptor activation. These results are in line with our previous in situ study that showed that microinjection of ATP within the PVN evoked a rapid and robust P2 receptor-mediated sympathoexcitatory response (Ferreira-Neto et al 2013).…”

Section: Discussionsupporting

confidence: 93%

“…Importantly, ATP has been shown to act as a cotransmitter with glutamate (Braga et al 2007;Pankratov et al 1998Pankratov et al , 2002Passamani et al 2011;Scislo and O'Leary 2000), and we recently showed that ATP-evoked sympathoexcitatory responses within the PVN were blunted in the presence of ionotropic glutamate receptor blockade (Ferreira-Neto et al 2013). Similar to this previous study, we found here that the ionotropic glutamatergic receptor antagonist KYN abolished the ATP-evoked increase in firing activity in PVN sympathetic neurons.…”

Section: Discussionsupporting

confidence: 89%

“…In the last five decades, ATP has emerged as an important neurotransmitter in several brain nuclei, including the hypothalamus (Burnstock 2007). Previous studies have shown that purinergic signaling in the PVN influences autonomic and neuroendocrine outflows (Cruz et al 2010;Ferreira-Neto et al 2013;Kapoor and Sladek 2000;Knott et al 2008;Li et al 2010;Mori et al 1992;Song and Sladek 2006). Our results demonstrate that exogenous ATP increases the firing activity of PVN sympathetic neurons, an effect that was dependent on P2 receptor activation.…”

Section: Discussionmentioning

confidence: 99%

“…Our previous study demonstrated that ATPinduced sympathoexcitation at the PVN level depends on non-NMDA receptors (Ferreira-Neto et al 2013). Thus we aimed to directly evaluate whether ATP affected AMPA receptor-mediated currents in PVN sympathetic neurons after focally applying AMPA onto those neurons, an approach that activates both synaptic and extrasynaptic receptors.…”

Section: Exogenous Atp Evokes Action Potentials In Pvn-rvlm Neurons Vmentioning

confidence: 99%

“…This is in fact supported by our recent studies showing that P2 receptor activation within the PVN stimulated sympathetic nerve activity. Importantly, we found that ATP-induced sympathoexcitation within the PVN involved interactions between P2 receptors and non-Nmethyl-D-aspartate (NMDA) glutamate receptors in the PVN (Ferreira-Neto et al 2013), suggesting a significant role of the purino-glutamatergic neurotransmission within the PVN in the central regulation of sympathetic outflow. However, the precise cellular mechanisms underlying the ATP-glutamate interaction in the PVN and whether this interaction contributed to osmotically driven PVN sympathetic neuronal activity are still unknown.…”

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confidence: 95%

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ATP stimulates rat hypothalamic sympathetic neurons by enhancing AMPA receptor-mediated currents

Ferreira‐Neto

Antunes

Stern

2015

Journal of Neurophysiology

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Ferreira-Neto HC, Antunes VR, Stern JE. ATP stimulates rat hypothalamic sympathetic neurons by enhancing AMPA receptormediated currents. J Neurophysiol 114: 159 -169, 2015. First published April 22, 2015 doi:10.1152/jn.01011.2014.-We have previously shown that ATP within the paraventricular nucleus (PVN) induces an increase in sympathetic activity, an effect attenuated by the antagonism of P2 and/or glutamatergic receptors. Here, we evaluated precise cellular mechanisms underlying the ATP-glutamate interaction in the PVN and assessed whether this receptor coupling contributed to osmotically driven sympathetic PVN neuronal activity. Whole-cell patch-clamp recordings obtained from PVN-rostral ventrolateral medulla neurons showed that ATP (100 M, 1 min, bath applied) induced an increase in firing rate (89%), an effect blocked by kynurenic acid (1 mM) or 4-[[4-Formyl-5-hydroxy-6-methyl-3-[(phosphonooxy)methyl]-2-pyridinyl]azo]-1,3-benzenedisulfonic acid tetrasodium salt (PPADS) (10 M). Whereas ATP did not affect glutamate synaptic function, ␣-amino-3-hydroxy-5-methylisoxazole propionic acid (AMPA) receptor-mediated currents evoked by focal application of AMPA (50 M, n ϭ 13) were increased in magnitude by ATP (AMPA amplitude: 33%, AMPA area: 52%). ATP potentiation of AMPA currents was blocked by PPADS (n ϭ 12) and by chelation of intracellular Ca 2ϩ (BAPTA, n ϭ 10). Finally, a hyperosmotic stimulus (mannitol 1%, ϩ55 mosM, n ϭ 8) potentiated evoked AMPA currents (53%), an effect blocked by PPADS (n ϭ 6). Taken together, our data support a functional stimulatory coupling between P2 and AMPA receptors (likely of extrasynaptic location) in PVN sympathetic neurons, which is engaged in response to an acute hyperosmotic stimulus, which might contribute in turn to osmotically driven sympathoexcitatory responses by the PVN.ATP; ␣-amino-3-hydroxy-5-methylisoxazole propionic acid; paraventricular nucleus; rostral ventrolateral medulla; hyperosmolarity BODY FLUID HOMEOSTASIS is tightly regulated by the integration of renal, cardiovascular, and neuroendocrine systems (Share and Claybaugh 1972). An increase in plasma osmolality induces several responses including an increase in sympathetic activity, blood pressure elevation, and the release of neurohormones, such as vasopressin and angiotensin II (Bealer 2000;Hatzinikolaou et al. 1980Hatzinikolaou et al. , 1981Stocker and Toney 2005;Weiss et al. 1996). Part of these responses are mediated through activation of the hypothalamic paraventricular nucleus (PVN) driven by the circumventricular organs in which central osmoreceptors are located (Antunes-Rodrigues et al. 2004;Stocker et al. 2008). The PVN is composed of magnocellular and parvocellular neurons. Magnocellular neurons synthesize and release vasopressin and oxytocin systemically from the posterior pituitary, whereas parvocellular neurons project to premotor sympathoexcitatory neurons located either in the rostral ventrolateral medulla (RVLM) and/or intermediolateral cell column of the spinal cord.Several neurotransmitters in t...

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Exogenous Atp Evokes Action Potentials In Pvn-rvlm Neurons Vmentioning

confidence: 99%

mentioning

confidence: 95%

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ATP stimulates rat hypothalamic sympathetic neurons by enhancing AMPA receptor-mediated currents

Ferreira‐Neto

Antunes

Stern

2015

Journal of Neurophysiology

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Purinoceptor: a novel target for hypertension

Zhu

et al. 2022

Purinergic Signalling

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Hypertension is the leading cause of morbidity and mortality globally among all cardiovascular diseases. Purinergic signalling plays a crucial role in hypertension through the sympathetic nerve system, neurons in the brain stem, carotid body, endothelium, immune system, renin-angiotensin system, sodium excretion, epithelial sodium channel activity (ENaC), and renal autoregulation. Under hypertension, adenosine triphosphate (ATP) is released as a cotransmitter from the sympathetic nerve. It mediates vascular tone mainly through P2X1R activation on smooth muscle cells and activation of P2X4R and P2YR on endothelial cells and also via interaction with other purinoceptors, showing dual effects. P2Y1R is linked to neurogenic hypertension. P2X7R and P2Y11R are potential targets for immune-related hypertension. P2X3R located on the carotid body is the most promising novel therapeutic target for hypertension. A1R, A2AR, A2BR, and P2X7R are all related to renal autoregulation, which contribute to both renal damage and hypertension. The main focus is on the evidence addressing the involvement of purinoceptors in hypertension and therapeutic interventions.

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Purinergic signaling pathways in endocrine system

Bjelobaba

Janjic

Stojilković

2015

Autonomic Neuroscience

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Adenosine-5′-triphosphate is released by neuroendocrine, endocrine, and other cell types and acts as an extracellular agonist for ligand-gated P2X cationic channels and G protein-coupled P2Y receptors in numerous organs and tissues, including the endocrine system. The breakdown of ATP by ectonucleotidases not only terminates its extracellular messenger functions, but also provides a pathway for the generation of two additional agonists: adenosine 5′-diphosphate, acting via some P2Y receptors, and adenosine, a native agonist for G protein-coupled adenosine receptors, also expressed in the endocrine system. This article provides a review of purinergic signaling pathways in the hypothalamic magnocellular neurosecretory cells and neurohypophysis, hypothalamic parvocellular neuroendocrine system, adenohypophysis, and effector glands organized in five axes: hypothalamic-pituitary-gonadal, hypothalamic-pituitary-thyroid, hypothalamic-pituitary-adrenal, hypothalamic-pituitary-growth hormone, and hypothalamic-pituitary-prolactin. We attempted to summarize current knowledge of purinergic receptor subtypes expressed in the endocrine system, including their roles in intracellular signaling, hormone secretion, and other cell functions. We also briefly review the release mechanism for adenosine-5′-triphosphate by neuroendocrine, endocrine and surrounding cells, the enzymes involved in adenosine-5′-triphosphate hydrolysis to adenosine-5′-diphosphate and adenosine, and the relevance of this pathway for sequential activation of receptors and termination of signaling.

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Purinergic and glutamatergic interactions in the hypothalamic paraventricular nucleus modulate sympathetic outflow

Cited by 12 publications

References 60 publications

ATP stimulates rat hypothalamic sympathetic neurons by enhancing AMPA receptor-mediated currents

ATP stimulates rat hypothalamic sympathetic neurons by enhancing AMPA receptor-mediated currents

Purinoceptor: a novel target for hypertension

Purinergic signaling pathways in endocrine system

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