Co-transmitter function of ATP in central catecholaminergic neurons of the rat

ATP is released during hypoxia from the ventrolateral medulla (VLM) and activates purinergic P2 receptors (P2Rs) at unknown loci to offset the secondary hypoxic depression of breathing. In this study, we used rhythmically active medullary slices from neonatal rat to map, in relation to anatomical and molecular markers of the pre-Bötzinger complex (preBötC) (a proposed site of rhythm generation), the effects of ATP on respiratory rhythm and identify the P2R subtypes responsible for these actions. Unilateral microinjections of ATP in a three-dimensional grid within the VLM revealed a "hotspot" where ATP (

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“…Slices lack many potential sources of ATP including pontine noradrenergic cell groups (Nieber et al, 1997;Poelchen et al, 2001). It is Figure 9.…”

Section: Physiological Role For P2r Signaling In Respiratory Controlmentioning

confidence: 99%

P2Y₁Receptor Modulation of the Pre-Bötzinger Complex Inspiratory Rhythm Generating NetworkIn Vitro

Lorier¹,

Huxtable²,

Robinson³

et al. 2007

J. Neurosci.

154

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“…ATP can also be co-released with and modulate the response to other neurotransmitters. As examples, hypoxic signaling in the rat carotid body results from the co-release of ATP and acetylcholine from type 1 chemoreceptor cells (Zhang et al, 2000), the co-release of ATP and norepinephrine evoke a rise in intracellular Ca 2+ in supraoptic nucleus neurons (Espallergues et al, 2007), and ATP and noradrenaline co-release from recurrent axon collaterals evoke excitation in locus coeruleus neurons (Poelchen et al, 2001). …”

Section: Introductionmentioning

confidence: 99%

ATP facilitates glutamatergic neurotransmission to cardiac vagal neurons in the nucleus ambiguus

et al. 2008

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Recent work has shown Adenosine 5'-triphosphate (ATP) plays an important role in modulating the activity of parasympathetic cardiac vagal neurons that dominate the neural control of heart rate. This study examined the mechanisms by which activation of ATP receptors modulates excitatory neurotransmission to cardiac vagal neurons. Glutamatergic activity to cardiac vagal neurons was isolated and examined using whole-cell patch-clamp recordings in an in vitro brain slice preparation in rats. ATP (100 μM) evoked increases in the frequency of glutamatergic miniature excitatory postsynaptic currents (mEPSCs) in cardiac vagal neurons which were blocked by the broad P2 receptor antagonist pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS, 100 μM). Application of the selective P2X receptor agonist, α, β-methylene ATP (100 μM), also increased glutamatergic mEPSC neurotransmission to cardiac vagal neurons indicating P2X receptors enhance glutamatergic release to cardiac vagal neurons. The evoked increase in glutamatergic mEPSC was unaltered by the voltage gated calcium channel blocker cadmium, and was abolished by the selective P2X receptor antagonist 2′,3′-O-(2,4,6-Trinitrophenyl) adenosine 5′-triphosphate, TNP-ATP (100 μM). This work demonstrates that the ATP evoked facilitation of excitatory neurotransmission to cardiac vagal neurons is dependent upon activation of P2X receptors on glutamatergic presynaptic terminals.

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“…In electrophysiological studies, a ,b-methylene-ATP excited LC neurons in the rat pontine slice preparation (30 -32). Furthermore, it was reported that ATP and noradrenaline are co-released in the LC (33). Thus, the goal of the present study was to determine the involvement of central NA neurons arising from the LC in the supraspinal antinociception by a ,b-methylene-ATP.…”

Section: Introductionmentioning

confidence: 90%

Involvement of Locus Coeruleus Noradrenergic Neurons in Supraspinal Antinociception by α,β-Methylene-ATP in Rats

et al. 2004

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Abstract. We reported previously that intracerebroventricular (i.c.v.) administration of P2X-receptor agonists produced antinociception and the effect was attenuated by i.c.v. pretreatment with b 2 -adrenergic receptor antagonists. The present study examined the involvement of noradrenergic neurons arising from the locus coeruleus (LC) in the supraspinal antinociception by the P2X-receptor agonist a ,b-methylene-ATP in rats. We found that pretreatment with DSP-4 (50 mg / kg, i.p.), which is a neurotoxin to selectively disrupt noradrenergic neurons arising from the LC, significantly attenuated the antinociception by i.c.v. administration of a ,b -methylene-ATP (10 nmol / rat). Microinjection of a ,b-methylene-ATP (0.1 and 1 nmol / side) into the bilateral LC significantly elevated the nociceptive threshold more potently than the i.c.v. administration at a dose of 10 nmol / rat. The antinociception by intra-LC injection of a ,b -methylene-ATP (1 nmol / side) was significantly attenuated by co-injection of pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (1 nmol / side), a non-selective P2X-receptor antagonist. These results suggest that noradrenergic neurons arising from the LC are involved in the supraspinal antinociception by a ,b -methylene-ATP through P2X receptors in the LC.

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Co-transmitter function of ATP in central catecholaminergic neurons of the rat

Cited by 82 publications

References 47 publications

P2Y₁Receptor Modulation of the Pre-Bötzinger Complex Inspiratory Rhythm Generating NetworkIn Vitro

P2Y₁Receptor Modulation of the Pre-Bötzinger Complex Inspiratory Rhythm Generating NetworkIn Vitro

ATP facilitates glutamatergic neurotransmission to cardiac vagal neurons in the nucleus ambiguus

Involvement of Locus Coeruleus Noradrenergic Neurons in Supraspinal Antinociception by α,β-Methylene-ATP in Rats

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Co-transmitter function of ATP in central catecholaminergic neurons of the rat

Cited by 82 publications

References 47 publications

P2Y1Receptor Modulation of the Pre-Bötzinger Complex Inspiratory Rhythm Generating NetworkIn Vitro

P2Y1Receptor Modulation of the Pre-Bötzinger Complex Inspiratory Rhythm Generating NetworkIn Vitro

ATP facilitates glutamatergic neurotransmission to cardiac vagal neurons in the nucleus ambiguus

Involvement of Locus Coeruleus Noradrenergic Neurons in Supraspinal Antinociception by α,β-Methylene-ATP in Rats

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P2Y₁Receptor Modulation of the Pre-Bötzinger Complex Inspiratory Rhythm Generating NetworkIn Vitro

P2Y₁Receptor Modulation of the Pre-Bötzinger Complex Inspiratory Rhythm Generating NetworkIn Vitro