Brainstem amino acid neurotransmitters and hypoxic ventilatory response

Hoop, B.; Beagle, John; Maher, Timothy J.; Kazemi, Homayoun

doi:10.1016/s0034-5687(99)00072-9

Cited by 44 publications

(30 citation statements)

References 28 publications

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“…Administration of GABA along with hypoxic stimulation may produce a balance between inhibitory and excitatory neurotransmitters, however it does not cause a disruption in the hypoxic response, as in the present study. The increase in glutamate and GABA in the phase in which ventilation increases during hypoxia (Hoop et al 1999;Richter et al 1999) and the increase in GABA in vivo and in vitro in hypoxia (Wood et al 1968;Iversen et al 1983;Madl et al 2000) also support this unexpected finding. Thus, the hypothesis that glutamate is solely responsible for the increase in acute sustained hypoxic response while GABA is responsible of acute sustained hypoxic depression (Chiang et al 1986;McCrimmon et al 1989;Kazemi and Hoop 1991) seems to weaken.…”

Section: Discussionmentioning

confidence: 60%

“…Inhibition of glutamate with specific antagonists almost totally abolishes the hyperventilatory response to hypoxia (Soto-Arape et al 1995). On the other hand, it was shown that glutamate and GABA concentrations increase simultaneously in the extracellular fluid of ventral medullary respiratory group during the hyperventilation observed in the first few minutes of hypoxia (Hoop et al 1999;Richter et al 1999). As it is well known, under normal conditions GABA is synthesized from glutamate by the effect of GAD, and the extracellular concentration of GABA is kept very low by GABA transporters.…”

Section: Discussionmentioning

confidence: 99%

“…These studies (Hoop et al 1999;Richter et al 1999) suggested that simultaneous increases in both glutamate and GABA during hypoxia may also play an important role in acute sustained hypoxia and in the occurrence of hypoxic ventilatory depression (HVD). The disruption of the balance between excitator and inhibitor neurotransmitters may affect the response for respiratory-related neurons.…”

Section: Discussionmentioning

confidence: 99%

“…In our study, when ICV glutamate antagonist (MK-801) was administrated, the hypoxic hyperventilatory responses seen in both groups were abolished. It was shown that acute hypoxia increases glutamate turnover (Hoop et al 1999;Richter et al 1999). Respiratory neurons receive glutamergic tonic inputs, which activate both NMDA and AMPA receptors (Haji et al 2000).…”

Section: Discussionmentioning

confidence: 99%

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The Role of Gamma-Aminobutyric Acid and Glutamate for Hypoxic Ventilatory Response in Anesthetized Rabbits

Yelmen

2004

Tohoku J. Exp. Med.

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Acute hypoxia produces an increase in ventilation. When the hypoxia is sustained, the initial increase in ventilation is followed by a decrease in ventilation. Hypoxia causes changes in brain neurotransmitters depending on its severity and durations. The purpose of this study was to investigate the role of gamma-aminobutyric acid (GABA) and glutamate for hypoxic ventilatory response in rabbits. The experiments were performed in peripheral chemoreceptors intact and denervated rabbits anesthetized with Na-pentobarbitate. For intracerebroventricular (ICV) injections of reagents in each animal, cannula was placed in left lateral cerebral ventricle by stereotaxic method. After ICV injection of GABA (0.48 mg/kg), air breathing in both groups caused a depression of respiratory activity. On the other hand, after ICV injection of GABA, breathing of hypoxic gas mixture (8% O 2 -92% N 2 ) in both groups produced the hypoxic hyperventilation. After ICV injection of GABA, blockade of GABA A receptors with bicuculline (0.2 mg/kg) did not prevent the hypoxic hyperventilation. In contrast, after ICV GABA injection, blockade of glutamate NMDA receptors with MK-801 (0.09 mg/kg) completely abolished the hypoxic hyperventilation observed while the animals were breathing hypoxic gas mixture. Our findings suggest that ICV injection of GABA causes respiratory depression in normoxic conditions, and that it increases ventilation in hypoxic conditions with or without peripheral chemoreceptor impulses by increasing glutamate.GABA; hypoxia; control of breathing; bicuculline; MK-801

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Section: Discussionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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The Role of Gamma-Aminobutyric Acid and Glutamate for Hypoxic Ventilatory Response in Anesthetized Rabbits

Yelmen

2004

Tohoku J. Exp. Med.

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“…It has been well documented that central amino acids change concentrations during hypoxia, and several studies have demonstrated that GABA is a major inhibitory amino acid neurotransmitter and is a central depressant of ventilation (18,19,26,27).…”

Section: Discussionmentioning

confidence: 99%

Brainstem Amino Acid Neurotransmitters and Ventilatory Response to Hypoxia in Piglets

et al. 2008

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ABSTRACT:The ventilatory response to hypoxia is influenced by the balance between inhibitory (GABA, glycine, and taurine) and excitatory (glutamate and aspartate) brainstem amino acid (AA) neurotransmitters. To assess the effects of AA in the nucleus tractus solitarius (NTS) on the ventilatory response to hypoxia at 1 and 2 wk of age, inhibitory and excitatory AA were sampled by microdialysis in unanesthetized and chronically instrumented piglets. Microdialysis samples from the NTS area were collected at 5-min intervals and minute ventilation (V E ), arterial blood pressure (ABP), and arterial blood gases (ABG) were measured while the animals were in quiet sleep. A biphasic ventilatory response to hypoxia was observed in wk 1 and 2, but the decrease in V E at 10 and 15 min was more marked in wk 1. This was associated with an increase in inhibitory AA during hypoxia in wk 1. Excitatory AA levels were elevated during hypoxia in wk 1 and 2. Changes in ABP, pH, and ABG during hypoxia were not different between weeks. These data suggest that the larger depression in the ventilatory response to hypoxia observed in younger piglets is mediated by predominance of the inhibitory AA neurotransmitters, GABA, glycine, and taurine, in the NTS. T he difference in ventilatory response to hypoxia between neonatal and adult subjects is well documented (1-3). The ventilatory response to hypoxia during the neonatal period is characterized by an increase in ventilation (1-2 min) followed by a decrease in minute ventilation (V E ) to values below or close to baseline levels. In contrast, a more sustained ventilatory response to hypoxia is described in adults (4). The initial increase in ventilation is mediated by the peripheral chemoreceptors, whereas subsequent changes are centrally mediated (5,6).The change from the neonatal to the adult ventilatory response is thought to occur during early postnatal life in most species (7,8). Previous studies have demonstrated that this change in the ventilatory response occurs within the first 1-2 wk of life in piglets (9 -11).Several mechanisms may be responsible for the ventilatory depression observed during hypoxia soon after birth. These include deterioration in lung mechanics (12), changes in metabolism (13), and a predominance of inhibitory over excitatory neurotransmitters in the CNS (14). Previous studies from our laboratory have demonstrated a role for amino acids (AA) in the hypoxic ventilatory response in newborn animals (5,(15)(16)(17). The balance between excitatory AA, such as glutamate and aspartate, and inhibitory AA, such as GABA and glycine, may influence the ventilatory response to hypoxia in the neonatal and postnatal periods. In newborn animals, it has been suggested that the increase in the release of the CNS inhibitory amino acid neurotransmitter GABA may be responsible for the hypoxic ventilatory depression (9,16,18). However, it is also possible that the biphasic response in ventilation during hypoxia may be due to a reduction in the release of central excitatory AA neur...

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Time Domains of the Hypoxic Ventilatory Response and Their Molecular Basis

Pamenter

Powell

2016

Comprehensive Physiology

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Ventilatory responses to hypoxia vary widely depending on the pattern and length of hypoxic exposure. Acute, prolonged, or intermittent hypoxic episodes can increase or decrease breathing for seconds to years, both during the hypoxic stimulus, and also after its removal. These myriad effects are the result of a complicated web of molecular interactions that underlie plasticity in the respiratory control reflex circuits and ultimately control the physiology of breathing in hypoxia. Since the time domains of the physiological hypoxic ventilatory response (HVR) were identified, considerable research effort has gone toward elucidating the underlying molecular mechanisms that mediate these varied responses. This research has begun to describe complicated and plastic interactions in the relay circuits between the peripheral chemoreceptors and the ventilatory control circuits within the central nervous system. Intriguingly, many of these molecular pathways seem to share key components between the different time domains, suggesting that varied physiological HVRs are the result of specific modifications to overlapping pathways. This review highlights what has been discovered regarding the cell and molecular level control of the time domains of the HVR, and highlights key areas where further research is required. Understanding the molecular control of ventilation in hypoxia has important implications for basic physiology and is emerging as an important component of several clinical fields.

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Brainstem amino acid neurotransmitters and hypoxic ventilatory response

Cited by 44 publications

References 28 publications

The Role of Gamma-Aminobutyric Acid and Glutamate for Hypoxic Ventilatory Response in Anesthetized Rabbits

The Role of Gamma-Aminobutyric Acid and Glutamate for Hypoxic Ventilatory Response in Anesthetized Rabbits

Brainstem Amino Acid Neurotransmitters and Ventilatory Response to Hypoxia in Piglets

Time Domains of the Hypoxic Ventilatory Response and Their Molecular Basis

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