The pre-Bötzinger complex and phase-spanning neurons in the adult rat

Sun, Qi; Goodchild, Ann K.; Chalmers, John; Pilowsky, Paul M.

doi:10.1016/s0006-8993(98)00872-5

Cited by 87 publications

(82 citation statements)

References 34 publications

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“…Another possible explanation for these respiratory responses is that the CVLM is intermingled with neurons in the preBötzinger complex (preBötC), a site regarded as the rhythm generator for breathing (29,44,47). Respiratory neurons in the ventral respiratory column are likely to provide inputs to nearby cardiovascular neurons (35,48).…”

Section: Discussionmentioning

confidence: 99%

Catestatin, a chromogranin A-derived peptide, is sympathoinhibitory and attenuates sympathetic barosensitivity and the chemoreflex in rat CVLM

Gaede

Pilowsky

2012

American Journal of Physiology-Regulatory, Integrative and Comp

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Gaede AH, Pilowsky PM. Catestatin, a chromogranin A-derived peptide, is sympathoinhibitory and attenuates sympathetic barosensitivity and the chemoreflex in rat CVLM. Am J Physiol Regul Integr Comp Physiol 302: R365-R372, 2012. First published November 30, 2011 doi:10.1152/ajpregu.00409.2011.-Hypertension is a major cause of morbidity. The neuropeptide catestatin [human chromogranin A-(352-372)] is a peptide product of the vesicular protein chromogranin A. Studies in the periphery and in vitro studies show that catestatin blocks nicotine-stimulated catecholamine release and interacts with ␤-adrenoceptors and histamine receptors. Catestatin immunoreactivity is present in the rostral ventrolateral medulla (RVLM), a key site for blood pressure control in the brain stem. Recently, we reported that microinjection of catestatin into the RVLM is sympathoexcitatory and increases barosensitivity. Here, we report the effects of microinjection of catestatin (1 mM, 50 nl) into the caudal ventrolateral medulla (CVLM) in urethane-anesthetized, bilaterally vagotomized, artificially ventilated Sprague-Dawley rats (n ϭ 8). We recorded resting arterial pressure, splanchnic sympathetic nerve activity, phrenic nerve activity, heart rate, and measured cardiovascular homeostatic reflexes. Homeostatic reflexes were evaluated by measuring cardiovascular responses to carotid baroreceptor and peripheral chemoreceptor activation. Catestatin decreased basal levels of arterial pressure (Ϫ23 Ϯ 4 mmHg), sympathetic nerve activity (-26.6 Ϯ 5.7%), heart rate (Ϫ19 Ϯ 5 bpm), and phrenic nerve amplitude (Ϫ16.8 Ϯ 3.3%). Catestatin caused a 15% decrease in phrenic inspiratory period (T i) and a 16% increase in phrenic expiratory period (Te) but had no net effect on the phrenic interburst interval (Ttot). Catestatin decreased sympathetic barosensitivity by 63.6% and attenuated the peripheral chemoreflex (sympathetic nerve response to brief hypoxia; range decreased 39.9%; slope decreased 30.1%). The results suggest that catestatin plays an important role in central cardiorespiratory control. hypertension; hypoxic chemoreflex; neuropeptides; neuropharmacology SYMPATHETIC TONE, AND THE INTEGRATION of adaptive reflexes, is dependent on bulbospinal presympathetic excitatory neurons in the rostral ventrolateral medulla oblongata (RVLM). Presympathetic sympathoexcitatory neurons integrate information from the center and periphery (7).Chromogranin A (CgA) is packaged into large dense core secretory vesicles in nerve terminals throughout the peripheral and central nervous systems (45), but the function of this protein remains unclear. CgA is the precursor of several biologically active peptides that may play an important autocrine regulatory role in the neuroendocrine system (1, 12). One such cleavage product of CgA, catestatin, was first isolated from bovine adrenal medullary chromaffin cells, and, initially, it was shown to act as a potent noncompetitive nicotinic acetylcholine receptor (nAChR) antagonist (24), and a ␤-adrenoceptor agonist in peripheral ...

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Section: Discussionmentioning

confidence: 99%

Catestatin, a chromogranin A-derived peptide, is sympathoinhibitory and attenuates sympathetic barosensitivity and the chemoreflex in rat CVLM

Gaede

Pilowsky

2012

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Histological analysis revealed that our microinjections were concentrated within the Bo « tzinger and pre-Bo « tzinger complexes. Studies in the rat have shown that there are predominantly expiratory neurones in the Bo « tzinger complex (80%) and that at least more than half of the neurones in the pre-Bo « tzinger complex are expiratory or of the phase spanning IE (inspiratory o¡-switch) type (Sun et al, 1998). Our previous electrophysiological data indicate that whilst ATP causes a generalised excitation of respiratory neurones within the VLM, irrespective of neuronal type and whether they are associated with driving inspiration or expiration, ATP was more e¡ective in increasing activity in post-inspiratory and expiratory neurones than inspiratory neurones .…”

Section: Discussionmentioning

confidence: 99%

Evidence for the involvement of purinergic signalling in the control of respiration

et al. 2001

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AbstractöThe ventrolateral medulla has a critical role in the generation and patterning of respiration via an extensive network of respiratory neurones. We have investigated the e¡ects of activating purinergic P2 receptors within the ventrolateral medulla of the anaesthetised rat on the overall pattern of respiratory activity. In addition, using immunohistochemical techniques, we have identi¢ed the subtypes of P2X receptors in the ventrolateral medulla. Unilateral microinjection of ATP into the ventrolateral medulla reduced in a dose-dependent manner, or abolished, resting phrenic nerve discharge recorded as an indication of central inspiratory drive. ATP also elicited increases in blood pressure and variable changes in heart rate. These e¡ects were mimicked by microinjection of the P2X receptor agonist K,L-methylene ATP into the ventrolateral medulla. Whilst microinjection of suramin, a P2 receptor antagonist, had no e¡ect on resting cardiorespiratory variables it blocked the respiratory and cardiovascular e¡ects of ATP microinjected into the ventrolateral medulla. Immunohistochemical staining using IgG antibodies showed that P2X 1 , P2X 2 , P2X 5 and P2X 6 , but not P2X 3 , P2X 4 or receptor subunits were localised in the rostral ventrolateral medulla.Our results indicate that several P2X receptor subtypes are localised within areas of the ventrolateral medulla that are important for cardiorespiratory control (including the pre-Bo « tzinger and Bo «tzinger complexes), and that activation of these receptors can have profound e¡ects on both the cardiovascular and the respiratory networks. Our pharmacological data suggest that di¡erent P2X subunits in this region may co-assemble to form hetero-oligomeric assemblies as well as homomultimers within this region. ß

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“…(11)(12)(13) Respiratory neurons are categorized by the phasic nature of their discharge pattern with most neurons firing predominantly within either inspiration (I neurons) or expiration (E neurons). Further categorization is dependent upon their discharge pattern during their active phase (augmenting, decrementing or plateau) and their axonal trajectory (propriobulbar, bulbospinal premotor, cranial motoneuron).…”

Section: Potential Roles Of Pacemaker Neurons In the Respiratory Netwmentioning

confidence: 99%

“…In addition, some neurons (particularly in the preBotC) discharge through a phase transition. One such subset, termed pre-I neurons, (13) begin to fire late in expiration and continue throughout inspiration. These neurons may correspond to the pacemaker neurons visualized by Koshiya and Smith.…”

Section: Potential Roles Of Pacemaker Neurons In the Respiratory Netwmentioning

confidence: 99%

Unraveling the mechanism for respiratory rhythm generation

et al. 2000

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The pre-Bötzinger complex and phase-spanning neurons in the adult rat

Cited by 87 publications

References 34 publications

Catestatin, a chromogranin A-derived peptide, is sympathoinhibitory and attenuates sympathetic barosensitivity and the chemoreflex in rat CVLM

Catestatin, a chromogranin A-derived peptide, is sympathoinhibitory and attenuates sympathetic barosensitivity and the chemoreflex in rat CVLM

Evidence for the involvement of purinergic signalling in the control of respiration

Unraveling the mechanism for respiratory rhythm generation

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