Glutamate in the nucleus of the solitary tract activates  both ionotropic and metabotropic glutamate receptors

Foley, C. Michael; Moffitt, Julia A.; Hay, Meredith; Hasser, Eileen M.

doi:10.1152/ajpregu.1998.275.6.r1858

Cited by 43 publications

(62 citation statements)

References 18 publications

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“…Consistent with this explanation are the reports that bilateral blockade of glutamate receptors in the NTS are necessary to increase the baseline BP (24). Furthermore, blockade of ionotropic as well as metabotropic glutamate receptors in the NTS may be necessary to elevate baseline BP (11). We have previously shown that the concentrations of D-AP7 and NBQX used in this study are sufficient to block the responses to ionotropic glutamate-receptor agonists NMDA and AMPA, respectively (9,34).…”

Section: Discussionsupporting

confidence: 85%

“…However, other authors have also made similar observations. For example, blockade of ionotropic glutamate receptors by unilateral microinjections of kynurenic acid into the NTS did not elicit a significant increase in baseline BP (11). Perhaps compensatory mechanisms in the contralateral NTS prevent the baseline BP from rising.…”

Section: Discussionmentioning

confidence: 98%

“…On the other hand, exogenously microinjected glutamate may reach metabotropic receptors in the perisynaptic region as well as ionotropic receptors within the synapse. Therefore, blockade of ionotropic glutamate receptors alone is not sufficient to abolish the effects of exogenous glutamate; blockade of both ionotropic and metabotropic receptors may be necessary to abolish the response to exogenously injected glutamate into the NTS (11).…”

Section: Discussionmentioning

confidence: 99%

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Mechanism of cardiovascular effects of nociceptin microinjected into the nucleus tractus solitarius of the rat

Chitravanshi

Sapru

2005

American Journal of Physiology-Regulatory, Integrative and Comp

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.62, and 1.25 mmol/l of nociceptin into the medial nucleus tractus solitarius (mNTS) elicited decreases in mean arterial pressure (11 Ϯ 1.8, 20 Ϯ 2.1, 21.5 Ϯ 3.1, and 15.5 Ϯ 1.9 mmHg, respectively) and heart rate (14 Ϯ 2.7, 29 Ϯ 5.5, 39 Ϯ 5.2, and 17.5 Ϯ 3.1 beats/min, respectively). Because maximal responses were elicited by microinjections of 0.62 mmol/l nociceptin, this concentration was used for other experiments. Repeated microinjections of nociceptin (0.62 mmol/l) into the mNTS, at 20-min intervals, did not elicit tachyphylaxis. Bradycardia induced by microinjections of nociceptin into the mNTS was abolished by bilateral vagotomy. The decreases in mean arterial pressure and heart rate elicited by nociceptin into the mNTS were blocked by prior microinjections of the specific ORL1-receptor antagonist [N-Phe 1 ]-nociceptin-(1-13)-NH2 (9 mmol/l). Microinjections of the ORL1-receptor antagonist alone did not elicit a response. Prior combined microinjections of GABA A and GABAB receptor antagonists (2 mmol/l gabazine and 100 mmol/l 2-hydroxysaclofen, respectively) into the mNTS blocked the responses to microinjections of nociceptin at the same site. Prior microinjections of ionotropic glutamate receptor antagonists (2 mmol/l NBQX and 5 mmol/l D-AP7) also blocked responses to nociceptin microinjections into the mNTS. These results were confirmed by direct neuronal recordings. It was concluded that 1) nociceptin inhibits GABAergic neurons in the mNTS, 2) GABAergic neurons may normally inhibit the release of glutamate from the terminals of peripheral afferents in the mNTS, and 3) inhibition of GABAergic neurons by nociceptin results in an increase in the release of glutamate in the mNTS, which in turn elicits depressor and bradycardic responses via activation of ionotropic glutamate receptors on secondary mNTS neurons. bradycardia; depressor responses; opioid peptides THE PRESENCE OF A NOVEL G-protein-coupled receptor [opioid receptor-like receptor (ORL1) or OP 4 receptor] throughout the central nervous system has been repeatedly demonstrated (1, 3, 6, 12, 18, 20 -22). There is a high sequence similarity of this receptor with other opioid receptors (e.g., -, ␦-, and -receptors) (3,6,21,36). Nociceptin (orphanin FQ) (4, 25, 26), a heptadecapeptide, has been demonstrated to be an endogenous ligand of ORL1 receptor because of its high and selective affinity for this receptor and a very poor affinity for -, ␦-, and -opioid receptors. One notable difference between other opioid receptor agonists (e.g., endomorphins, enkephalins, and dynorphin A) and nociceptin is that naloxone blocks the effects of these opioid receptor agonists but not those of nociceptin (4,5,13,16,29).The presence of an endogenous ligand for ORL1 receptors (nociceptin or orphanin FQ) has been demonstrated throughout the central nervous system, including the nucleus tractus solitarius (NTS) (10, 23, 35). There are very few reports in which the cardiovascular effects of ORL1 receptor activation by nociceptin in the medial nucleus tractus solitarius (m...

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

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Mechanism of cardiovascular effects of nociceptin microinjected into the nucleus tractus solitarius of the rat

Chitravanshi

Sapru

2005

American Journal of Physiology-Regulatory, Integrative and Comp

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“…The effective dose and specific effect of Kyn on ionotropic glutamate receptors have been shown previously. 33 Bilateral microinjection of Kyn (0.15 to 5.0 nmol) into the PVN had no significant effect on the LSNA, MAP, and HR in 6 WKY rats. However, bilateral microinjection of Kyn (0.15 to 5.0 nmol/50 nL) into the PVN decreased the LSNA, MAP, and HR in 6 SHRs in a dose-dependent fashion ( Figure 5).…”

Section: Effect Of Microinjection Of Kyn Into the Pvnmentioning

confidence: 89%

“…We subsequently determined the effect of blockade of both NMDA and non-NMDA receptors by Kyn 15,27,33 in the PVN on sympathetic vasomotor tone in WKY rats and SHRs. The effective dose and specific effect of Kyn on ionotropic glutamate receptors have been shown previously.…”

Section: Effect Of Microinjection Of Kyn Into the Pvnmentioning

confidence: 99%

Glutamatergic Inputs in the Hypothalamic Paraventricular Nucleus Maintain Sympathetic Vasomotor Tone in Hypertension

2007

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Abstract-The paraventricular nucleus (PVN) of the hypothalamus is critical to the regulation of sympathetic output. The PVN hyperactivity is known to cause increased sympathetic nerve activity in spontaneously hypertensive rats (SHRs). The purpose of this study was to determine whether glutamatergic input to the PVN contributes to heightened sympathetic outflow in hypertension. Lumbar sympathetic nerve activity, mean arterial blood pressure, and heart rate were recorded from anesthetized SHRs and Wistar-Kyoto (WKY) rats. Bilateral microinjection of an N-methyl-Daspartate receptor antagonist, 2-amino-5-phosphonopentanoic acid, or a non-N-methyl-D-aspartate receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione, into the PVN dose-dependently decreased lumbar sympathetic nerve activity, mean arterial blood pressure, and heart rate in SHRs but not in WKY rats. Bilateral microinjection of kynurenic acid into the PVN also significantly decreased lumbar sympathetic nerve activity, mean arterial blood pressure, and heart rate in SHRs but not in WKY rats. Furthermore, microinjection of gabazine, a specific GABA A receptor antagonist, into the PVN increased lumbar sympathetic nerve activity, mean arterial blood pressure, and heart rate in both SHRs and WKY rats. Notably, this response was significantly attenuated in SHRs compared with that in WKY rats. In addition, kynurenic acid abolished the sympathoexcitatory and pressor responses to microinjection of gabazine into the PVN in both SHRs and WKY rats. Thus, this study provides new functional evidence that resting sympathetic vasomotor tone is maintained by tonic glutamatergic input in the PVN in SHRs. Removal of GABAergic inhibition results in augmented glutamatergic input in the PVN, which probably constitutes an important source of excitatory drive to the brain stem vasomotor neurons in hypertension. Key Words: excitatory amino acids Ⅲ hypothalamus Ⅲ sympathetic nervous system Ⅲ synaptic transmission Ⅲ autonomic nervous system Ⅲ NMDA receptors H ypertension is a significant risk factor for cardiovascular, renal, and cerebrovascular disorders. Increased sympathetic activity is often associated with hypertension and may contribute to the pathogenesis and maintenance of hypertension. 1,2 Previous studies suggested that altered central mechanisms are responsible for the elevated sympathetic outflow and arterial blood pressure in hypertension. In this regard, transection of the brain caudal to the hypothalamus reduces arterial blood pressure in spontaneously hypertensive rats (SHRs) but not in Wistar-Kyoto (WKY) rats. 3 The paraventricular nucleus (PVN) of the hypothalamus is an important region for the regulation of sympathetic output and arterial blood pressure. 4 -7 Lesions of the PVN in hypertensive rats, such as SHRs, Dahl salt-sensitive rats, and rats with renal hypertension, decrease blood pressure. 8 -11 Furthermore, inhibition of the PVN with muscimol reduces the blood pressure and sympathetic nerve activity in SHRs. 12 Thus, hyperactivity of PVN neurons may d...

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Heterogeneity of metabotropic glutamate receptors in autonomic cell groups of the medulla oblongata of the rat

et al. 1999

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Metabotropic glutamate receptors (mGluRs) in the medulla oblongata have been suggested to be involved in the regulation of autonomic function. The aim of the present study was to examine the localization and expression of four types of mGluRs: mGluR1a, mGluR2/3, mGluR5, and mGluR7 in the dorsal and ventral autonomic nuclei of the medulla of the rat. The four mGluR subtypes studied were differentially distributed in distinct subnuclei in the nucleus of the solitary tract (NTS). mGluR1a immunoreactivity was identified in cell bodies, dendrites, and axonal processes in the intermediate, dorsal lateral, and interstitial subnuclei of the NTS. No mGluR1a immunoreactivity was observed in the commissural or medial NTS subnuclei. Immunoreactivity for mGluR2/3 and mGluR5 as observed in fibers and putative axonal processes in the interstitial, intermediate, and dorsolateral subnuclei of the NTS. In contrast, mGluR7 was expressed primarily in fibers and terminals in the central and commissural NTS subnuclei. Expression of mGluR2/3 was clearly evident in cell bodies, dendrites, and axonal processes within the area postrema. The vagal outflow nuclei were also studied. The dorsal motor nucleus of the vagus (DMN) contained mGluR1a cell bodies, dendrites, and axonal fibers and light mGluR2/3 processes. Throughout the rostral‐caudal extent of the compact and semicompact formation nucleus ambiguus, mGluR1a was found in cell bodies and fibers. Within the caudal and rostral regions of the ventral lateral medulla, mGluR1a was observed in cell bodies and fibers. Cell bodies containing mGluR1a were found adjacent to cells staining positive for tyrosine hydroxylase (TH) in these regions but were not colocalized with the TH staining. However, mGluR1a‐expressing neurons in the ventral lateral medulla did appear to receive innervation from TH‐containing fibers. These results suggest that the mGluR1a‐expressing neurons within the ventral lateral medulla are predominantly not catecholaminergic but may be innervated by catecholamine‐containing fibers. These data are the first to provide a mapping of the different mGluR subtypes within the medulla and may facilitate predictions regarding the function of L‐glutamate neurotransmission in these regions. J. Comp. Neurol. 403:486–501, 1999. © 1999 Wiley‐Liss, Inc.

show abstract

Glutamate in the nucleus of the solitary tract activates both ionotropic and metabotropic glutamate receptors

Cited by 43 publications

References 18 publications

Mechanism of cardiovascular effects of nociceptin microinjected into the nucleus tractus solitarius of the rat

Mechanism of cardiovascular effects of nociceptin microinjected into the nucleus tractus solitarius of the rat

Glutamatergic Inputs in the Hypothalamic Paraventricular Nucleus Maintain Sympathetic Vasomotor Tone in Hypertension

Heterogeneity of metabotropic glutamate receptors in autonomic cell groups of the medulla oblongata of the rat

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