Glycine, like glutamate, microinjected into the nucleus tractus solitarii of rat decreases arterial pressure and heart rate

doi:10.1016/0006-8993(89)91388-7

Brain Research

Volume 477, Issues 1–2, 16 January 1989, Pages 7-13

https://doi.org/10.1016/0006-8993(89)91388-7 Get rights and content

Abstract

Glycinergic mechanisms have been implicated in central cardiovascular regulation. However, the inhibitory amino acid's role in the nucleus tractus solitarii (NTS), the site of termination of cardiovascular afferents, has not been clarified. Thus, we sought to determine if the microinjection of glycine into the NTS alters arterial pressure and heart rate. Microinjections of glycine, like glutamate, confined to the NTS decreased arterial pressure and heart rate in a neurally mediated, dose-dependent manner. The glycine antagonist strychnine completely blocked these effects of glycine but did not itself alter pressure or heart rate, or interfere with the baroreceptor reflex. The acute hypotensive, bradycardic response to glycine was followed by a period during which glycine essentially eliminated the cardiovascular responses to the microinjection into the NTS of glutamate, an amino acid reputed to be a transmitter in the baroreceptor reflex arc. These data suggest that glycine is involved in cardiovascular regulation by the NTS but do not support its being an integral transmitter in the baroreceptor reflex.

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Cited by (48)

Co-localisation of markers for glycinergic and GABAergic neurones in rat nucleus of the solitary tract: Implications for co-transmission
2010, Journal of Chemical Neuroanatomy
Immunoreactive structures visualised with antibodies to glycine were prominent in areas of the nucleus of the solitary tract (NTS) surrounding the tractus solitarius, but scarcer in medial and ventral areas of the nucleus. This contrasted with a higher density, more homogenous distribution of structures labelled for γ-aminobutyric acid (GABA). Immunolabelling of adjacent semi-thin sections nonetheless indicated a close correspondence between cells and puncta labelled by glycine and GABA antisera in certain NTS areas. With post-embedding electron microscopic immunolabelling, synaptic terminals with high, presumed transmitter levels of glycine were discriminated from terminals containing low, metabolic levels by quantitative analysis of gold particle labelling densities. In a random sample of terminals, 28.5% qualified on this basis as glycinergic (compared to 44.4% GABAergic); these glycinergic terminals targeted mainly dendritic structures and contained pleomorphic vesicles and symmetrical synapses. Serial section analysis revealed few terminals (5.2%) immunoreactive for glycine alone, with 82% of glycinergic terminals also containing high levels of GABA immunoreactivity. No evidence for co-localisation of glycine and glutamate was found. Light, confocal and electron microscopic labelling with antibodies to proteins specific for glycine and GABA synthesis, release and uptake confirmed that glycinergic terminals also containing GABA are found predominantly in more lateral areas of NTS, despite glycine receptors and the ‘glial’ glycine transporter (GLYT1) being expressed throughout all areas of the nucleus. The data suggest that synaptic terminals in certain functionally distinct areas of NTS co-release both inhibitory amino acids, which may account for the previously reported differential inhibitory effects of glycine and GABA on NTS neurones.
Optical approaches to embryonic development of neural functions in the brainstem
2001, Progress in Neurobiology
Citation Excerpt :
Furthermore, biochemical and histochemical investigations have demonstrated the presence of glycine in the NTS (Perrone, 1981; Cassell et al., 1992). Kubo and Kihara (1987) found that micro-injections of glycine into the medial area of the NTS of the rat led to an increase in arterial pressure and heart rate; while Talman and Robertson (1989) reported that glycine application in the NTS decreased arterial pressure and heart rate. Although the physiological action of glycine has not been clearly established, these studies suggest that glycine modulates cardiovascular control within the NTS.
The ontogenetic approach to physiological events is a useful strategy for understanding the functional organization/architecture of the vertebrate brainstem. However, conventional electrophysiological techniques are difficult or impossible to employ in the early embryonic central nervous system. Optical techniques using voltage-sensitive dyes have made it possible to monitor neural activities from multiple regions of living systems, and have proven to be a useful tool for analyzing the embryogenetic expression of brainstem neural function. This review describes recent progress in optical studies made on embryonic chick and rat brainstems. Several technical issues concerning optical recording from the embryonic brainstem preparations are discussed, and characteristics of the optical signals evoked by cranial nerve stimulation or occurring spontaneously are described. Special attention is paid to the chronological analyses of embryogenetic expression of brainstem function and to the spatial patterning of the functional organization/architecture of the brainstem nuclei. In addition, optical analyses of glutamate, GABA, and glycine receptor functions during embryogenesis are described in detail for the chick nucleus tractus solitarius. This review also discusses intrinsic optical signals associated with neuronal depolarization. Some emphases are also placed on the physiological properties of embryonic brainstem neurons, which may be of interest from the viewpoint of developmental neurobiology.
Distal and deglutitive inhibition in the rat esophagus: Role of inhibitory neurotransmission in the nucleus tractus solitarii
2000, Gastroenterology
Background & Aims: This study aimed to show the presence of deglutitive and distal inhibition in the rat esophagus and to differentiate the underlying neural mechanisms. Methods: Under urethane anesthesia, the pharyngoesophageal tract was fitted with water-filled balloons for luminal distention and pressure recording. Neural activity was recorded in the nucleus tractus solitarii subnucleus centralis and rostral nucleus ambiguus. Results: Distal esophageal distention evoked both rhythmic local contractions and burst discharges of ambiguus neurons that were simultaneously inhibited by a swallow or proximal esophageal distention. In subnucleus centralis interneurons, type I rhythmic burst discharges correlated with distal esophageal pressure waves and were suppressed by midthoracic esophageal distention; type II nonrhythmic excitatory responses, like type III inhibitory responses, were evoked by distention of either the thoracic or distal esophagus. When applied to the surface of the solitarius complex, bicuculline and, less effectively, strychnine suppressed distal inhibition, and 2-(OH)-saclofen and 3-aminopropylphosphonic acid were ineffective. None of the drugs tested, including systemic picrotoxin, affected deglutitive inhibition. Conclusions: Distal and deglutitive inhibition are present in the rat esophagus. The former, unlike the latter, depends on activation of ligand-gated chloride channels associated with subnucleus centralis premotor neurons. Inhibitory aminoacidergic local interneurons are a probable source of type II responses.
GASTROENTEROLOGY 2000;118:328-336
Glycine receptor (gephyrin) immunoreactivity is present on cholinergic neurons in the dorsal vagal complex
1999, Neuroscience
We previously demonstrated that microinjection of exogenous glycine into the nucleus tractus solitarii of anesthetized rats elicits responses that are qualitatively like those elicited by microinjection of acetylcholine at the same site. The responses to glycine, like those to acetylcholine, are blocked by administration of a muscarinic receptor antagonist and prolonged by administration of an acetylcholinesterase inhibitor. Furthermore, glycine leads to release of acetylcholine from the nucleus tractus solitarii and surrounding dorsal vagal complex. An anatomical framework for interactions between glycinergic and cholinergic neurons was established by studies that identified glycine terminals and receptors in the dorsal vagal complex. The current study investigated the relationship between glycine receptors and neuronal elements that were immunoreactive for choline acetyltransferase in the dorsal vagal complex. Neurons that were immunoreactive for choline acetyltransferase were located in the dorsal motor nucleus of the vagus, hypoglossal nucleus and nucleus ambiguus, and stained cells were also present in medial, intermediate, and ventrolateral subnuclei of the nucleus tractus solitarii. We found that glycine receptors, immunolabeled with an antibody to gephyrin, were present on cholinergic dendrites in the nucleus tractus solitarii. Gephyrin immunoreactivity was also present on dendrites that did not stain for choline acetyltransferase.
These data further support the contribution of cholinergic neurons in mediating cardiovascular responses to glycine in the nucleus tractus solitarii.
Kinetics of sevoflurane action on GABA- and glycine-induced currents in acutely dissociated rat hippocampal neurons
1998, Neuroscience
Effects of a new kind of volatile anaesthetics, sevoflurane, on GABA- and glycine-gated chloride current (I_Cl) were examined in single pyramidal neurons acutely dissociated from the rat hippocampal CA1 region, using the voltage-clamp mode of the nystatin-perforated patch-clamp technique. Rapid application of sevoflurane-induced I_Cl by itself, with the time to peak reduced as the sevoflurane concentration was increased from 10⁻³ to 3×10⁻³ M. Although a pretreatment with 10⁻³ M sevoflurane enhanced the peak amplitude of GABA (3×10⁻⁶ M)-induced I_Cl and suppressed the peak amplitude when the GABA concentration was increased to 10⁻⁴ M, the pretreatment decreased the time to peak of the I_Cl induced by any concentration of GABA (from 3×10⁻⁶ to 10⁻⁴ M). The treatment also accelerated the decay phase of the GABA-induced I_Cl. On the other hand, sevoflurane suppressed the peak I_Cl induced by 3×10⁻⁵ M glycine in a concentration-dependent manner. In the presence of 3×10⁻⁴ M sevoflurane, the peak amplitude of the glycine-induced I_Cl was decreased without changes in EC₅₀ or Hill coefficients. Pretreatment with 10⁻³ M sevoflurane did not affect the time to peak of the I_Cl induced by any concentration of glycine (from 3×10⁻⁵ to 10⁻³ M). Pretreatment with 3×10⁻⁸ M strychnine markedly prolonged the time to peak of the glycine-induced I_Cl.
These results suggest that sevoflurane modulated the amplitude of the GABA responses, depending on the balance of the accelerated activation and decay phases, and that sevoflurane suppressed the glycine-induced I_Cl in a non-competitive manner without noticeable effect on the kinetics. The reversible and differential modulation of GABA_A and glycine receptors might underlie a part of the anaesthetic actions and less adverse clinical effects of sevoflurane.
Glycine increases arterial pressure and augments NMDA-induced pressor responses in the dorsomedial and ventrolateral medulla of cats
1997, Journal of the Autonomic Nervous System
The present study is designed to determine and characterize two neurobiological events. Firstly, we investigated whether increases of systemic arterial pressure (SAP) and sympathetic vertebral nerve activity (VNA) produced by microinjection of glycine (Gly) in the dorsomedial (DM) or rostral ventrolateral medulla (RVLM) are mediated by pressor neurons in DM or RVLM. Secondly, we assessed whether simultaneous microinjections of Gly and N-methyl-d-aspartate (NMDA) in DM or RVLM potentiate the NMDA-pressor effects. Changes in SAP and VNA were recorded in 33 cats under α-chloralose and urethane anesthesia. Microinjection of sodium glutamate (Glu, 0.25 M, 30 nl) or Gly (1.0 M, 30 nl) into the DM or RVLM increased SAP and VNA in similar magnitude. Latencies of changes in SAP and VNA induced by Gly, however, were longer (3 s) than those induced by Glu. Prior microinjection of the following antagonists blocked the Gly-induced pressor responses: 2-amino-5-phosphonopentanoate (AP-5, 25 mM, 30 nl), a specific NMDA receptor antagonist; or glutamate diethyl ester (GDEE, 0.5 M, 30 nl), a quisqualate receptor antagonist; or kynurenic acid (KYN, 10 mM, 30 nl), a broad spectrum competitive Glu antagonist. Prior treatment with strychnine (3 mM, 30 nl), a specific Gly antagonist, also blocked the Gly-induced pressor responses. Since Gly is believed to be an inhibitory neurotransmitter, these data suggest that Gly may produce pressor actions via an inhibition on specific inhibitory neurons synapsing with the pressor neurons. NMDA (0.1 M, 30 nl) and Gly (1.0 M, 30 nl) microinjected simultaneously in DM or RVLM produced a greater pressor action than NMDA alone. This potentiation was blocked by KYN, another known antagonist for such potentiation, but was only partially blocked by strychnine.

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Research reportGlycine, like glutamate, microinjected into the nucleus tractus solitarii of rat decreases arterial pressure and heart rate

Abstract

Eur. J. Pharmacol.

Life Sci.

Neurosci. Lett.

Brain Research

Brain Research

Brain Research

Brain Research

Eur. J. Pharmacol.

Neurosci. Lett.

Brain Research

Brain Research

Life Sci.

Brain Research

Tonic and reflex functions of medullary sympathetic cardiovascular centers

J. Neurophysiol.

Glycine-induced changes in acetylcholine release from guinea pig brain slices

Br. J. Pharmacol.

Evidence for a neuromodulatory role of GABA at the first synapse of the baroreceptor reflex pathway. Effects of GABA derivatives injected into the NTS

Naunyn Schmiedeberg's Arch. Pharmacol.

Glycine-binding sites and NMDA receptors in brain

Nature (Lond.)

Studies of neurotransmitter actions (GABA, glycine, convulsants)

Research report
Glycine, like glutamate, microinjected into the nucleus tractus solitarii of rat decreases arterial pressure and heart rate