Differential role of ionotropic glutamatergic mechanisms  in responses to NTS P<sub>2x</sub> and A<sub>2a</sub> receptor stimulation

Scislo, Tadeusz J.; O’Leary, Donal S.

doi:10.1152/ajpheart.2000.278.6.h2057

Cited by 28 publications

(77 citation statements)

References 42 publications

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“…Although it was previously shown that activation of A2a receptors induces release of catecholamines by the adrenal medulla [45,54], we believe that P2 receptors also partly contribute to epinephrine release in response to activation of the HDA. The findings here differ from previous evidence of sympathoinhibition to the adrenal gland [21,45]. The discrepancy can be explained by the fact that adrenal sympathetic nerve activity regulates secretion of catecholamines related both to cardiovascular control and glucose metabolism [55].…”

Section: Hindlimb Vasodilation In Alerting-defense Responses Is Mediacontrasting

confidence: 99%

“…By contrast, it is known that the increase in HVC following activation of P2 receptors in NTS neurons supposedly results from a reduction in sympathetic nerve activity [21,45]. This discrepancy can be explained partly by excitatory projections from the NTS to inhibitory interneurons in the RVLM.…”

Section: Hindlimb Vasodilation In Alerting-defense Responses Is Mediamentioning

confidence: 93%

“…In fact, cardiovascular sympathetic responses to activation of P2 receptors in NTS neurons apparently depend on glutamatergic mechanisms within the NTS [21]. The blockade of glutamate receptors in NTS neurons presumably reduced the sympathoinhibition in response to activation of P2x receptors in the NTS by α,β-methylene ATP [21]. Microinjections of kynurenate into the NTS following suramin, on the other hand, did not cause further reduction in the evoked vasodilation.…”

Section: Hindlimb Vasodilation In Alerting-defense Responses Is Mediamentioning

confidence: 97%

“…Microinjections of kynurenate into the NTS blocked the cardiovascular changes elicited by either α,β-methylene ATP or glutamate, but suramin selectively blocked the cardiovascular effects to α,β-methylene ATP into the NTS. In fact, cardiovascular sympathetic responses to activation of P2 receptors in NTS neurons apparently depend on glutamatergic mechanisms within the NTS [21]. The blockade of glutamate receptors in NTS neurons presumably reduced the sympathoinhibition in response to activation of P2x receptors in the NTS by α,β-methylene ATP [21].…”

Section: Hindlimb Vasodilation In Alerting-defense Responses Is Mediamentioning

confidence: 99%

“…In addition, the role of medullary P2 receptors in the NTS and RVLM on cardiovascular responses to stimulation of the HDA still remains to be established. In the NTS, ATP apparently acts as a neuromodulator interacts with terminals promoting glutamate release [21], thus altering sympathetic nerve discharge. In fact, in vitro activation of purinergic P2 receptors located in the presynaptic membrane produces release of glutamate in the neuron terminal observed [22,23].…”

Section: Introductionmentioning

confidence: 99%

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Interaction of medullary P2 and glutamate receptors mediates the vasodilation in the hindlimb of rat

Korim

Ferreira-Neto

Pedrino

et al. 2012

Purinergic Signalling

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In the nucleus tractus solitarii (NTS) of rats, blockade of extracellular ATP breakdown to adenosine reduces arterial blood pressure (AP) increases that follow stimulation of the hypothalamic defense area (HDA). The effects of ATP on NTS P2 receptors, during stimulation of the HDA, are still unclear. The aim of this study was to determine whether activation of P2 receptors in the NTS mediates cardiovascular responses to HDA stimulation. Further investigation was taken to establish if changes in hindlimb vascular conductance (HVC) elicited by electrical stimulation of the HDA, or activation of P2 receptors in the NTS, are relayed in the rostral ventrolateral medulla (RVLM); and if those responses depend on glutamate release by ATP acting on presynaptic terminals. In anesthetized and paralyzed rats, electrical stimulation of the HDA increased AP and HVC. Blockade of P2 or glutamate receptors in the NTS, with bilateral microinjections of suramin (10 mM) or kynurenate (50 mM) reduced only the evoked increase in HVC by 75 % or more. Similar results were obtained with the blockade combining both antagonists. Blockade of P2 and glutamate receptors in the RVLM also reduced the increases in HVC to stimulation of the HDA by up to 75 %. Bilateral microinjections of kynurenate in the RVLM abolished changes in AP and HVC to injections of the P2 receptor agonist α,β-methylene ATP (20 mM) into the NTS. The findings suggest that HDA-NTS-RVLM pathways in control of HVC are mediated by activation of P2 and glutamate receptors in the brainstem in alerting-defense reactions.

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Section: Hindlimb Vasodilation In Alerting-defense Responses Is Mediacontrasting

confidence: 99%

Section: Hindlimb Vasodilation In Alerting-defense Responses Is Mediamentioning

confidence: 93%

Section: Hindlimb Vasodilation In Alerting-defense Responses Is Mediamentioning

confidence: 97%

Section: Hindlimb Vasodilation In Alerting-defense Responses Is Mediamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Interaction of medullary P2 and glutamate receptors mediates the vasodilation in the hindlimb of rat

Korim

Ferreira-Neto

Pedrino

et al. 2012

Purinergic Signalling

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

Ferreira‐Neto

Yao

Antunes

2013

Purinergic Signalling

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P2X receptors are expressed on ventrolateral medulla projecting paraventricular nucleus (PVN) neurons. Here, we investigate the role of adenosine 5′-triphosphate (ATP) in modulating sympathetic nerve activity (SNA) at the level of the PVN. We used an in situ arterially perfused rat preparation to determine the effect of P2 receptor activation and the putative interaction between purinergic and glutamatergic neurotransmitter systems within the PVN on lumbar SNA (LSNA). Unilateral microinjection of ATP into the PVN induced a dose-related increase in the LSNA (1 nmol: 38±6 %, 2.5 nmol: 72±7 %, 5 nmol: 96± 13 %). This increase was significantly attenuated by blockade of P2 receptors (pyridoxalphosphate-6-azophenyl-20,40-disulphonic acid, PPADS) and glutamate receptors (kynurenic acid, KYN) or a combination of both. The increase in LSNA elicited by L-glutamate microinjection into the PVN was not affected by a previous injection of PPADS. Selective blockade of non-Nmethyl-D-aspartate receptors (6-cyano-7-nitroquinoxaline-2,3-dione disodium salt, CNQX), but not N-methyl-D-aspartate receptors (NMDA) receptors (DL-2-amino-5-phosphonopentanoic acid, AP5), attenuated the ATP-induced sympathoexcitatory effects at the PVN level. Taken together, our data show that purinergic neurotransmission within the PVN is involved in the control of SNA via P2 receptor activation. Moreover, we show an interaction between P2 receptors and non-NMDA glutamate receptors in the PVN suggesting that these functional interactions might be important in the regulation of sympathetic outflow.

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Nucleus tractus solitarii A2a adenosine receptors inhibit cardiopulmonary chemoreflex control of sympathetic outputs

Minic¹,

O’Leary²,

Scislo³

2014

Autonomic Neuroscience

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Previously we have shown that stimulation of inhibitory A1 adenosine receptors located in the nucleus tractus solitarii (NTS) attenuates cardiopulmonary chemoreflex (CCR) evoked inhibition of renal, adrenal and lumbar sympathetic nerve activity and reflex decreases in arterial pressure and heart rate. Activation of facilitatory A2a adenosine receptors, which dominate over A1 receptors in the NTS, contrastingly alters baseline activity of regional sympathetic outputs: it decreases renal, increases adrenal and does not change lumbar nerve activity. Considering that NTS A2a receptors may facilitate release of inhibitory transmitters we hypothesized that A2a receptors will act in concert with A1 receptors differentially inhibiting regional sympathetic CCR responses (adrenal>lumbar>renal). In urethane/chloralose anesthetized rats (n=38) we compared regional sympathetic responses evoked by stimulation of the CCR with right atrial injections of serotonin 5HT3 receptor agonist, phenylbiguanide, (1–8 µg/kg) before and after selective stimulation, blockade or combined blockade and stimulation of NTS A2a adenosine receptors (microinjections into the NTS of CGS-21680 0.2–20 pmol/50 nl, ZM-241385 40 pmol/100 nl or ZM-241385+CGS-21680, respectively). We found that stimulation of A2a adenosine receptors uniformly inhibited the regional sympathetic and hemodynamic reflex responses and this effect was abolished by the selective blockade of NTS A2a receptors. This indicates that A2a receptor triggered inhibition of CCR responses and the contrasting shifts in baseline sympathetic activity are mediated via different mechanisms. These data implicate that stimulation of NTS A2a receptors triggers unknown inhibitory mechanism(s) which in turn inhibit transmission in the CCR pathway when adenosine is released into the NTS during severe hypotension.

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Differential role of ionotropic glutamatergic mechanisms in responses to NTS P_2x and A_2a receptor stimulation

Cited by 28 publications

References 42 publications

Interaction of medullary P2 and glutamate receptors mediates the vasodilation in the hindlimb of rat

Interaction of medullary P2 and glutamate receptors mediates the vasodilation in the hindlimb of rat

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

Nucleus tractus solitarii A2a adenosine receptors inhibit cardiopulmonary chemoreflex control of sympathetic outputs

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Differential role of ionotropic glutamatergic mechanisms in responses to NTS P2x and A2a receptor stimulation

Cited by 28 publications

References 42 publications

Interaction of medullary P2 and glutamate receptors mediates the vasodilation in the hindlimb of rat

Interaction of medullary P2 and glutamate receptors mediates the vasodilation in the hindlimb of rat

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

Nucleus tractus solitarii A2a adenosine receptors inhibit cardiopulmonary chemoreflex control of sympathetic outputs

Contact Info

Product

Resources

About

Differential role of ionotropic glutamatergic mechanisms in responses to NTS P_2x and A_2a receptor stimulation