Endothelin‐1 as a neuropeptide: neurotransmitter or neurovascular effects?

Dashwood, Michael R.; Loesch, Andrzej

doi:10.1007/s12079-009-0073-3

Cited by 41 publications

(28 citation statements)

References 123 publications

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“…Although the above findings suggest that ET-1 may play a neuromodulatory role in the hypothalamus, the absence of a direct demonstration on synaptic efficacy has led to speculation that the effects of ET-1 on neurohormone release are due to its neurovascular actions (Dashwood and Loesch, 2010), resulting in depolarization subsequent to local ischemia (Pittman and Mulligan, 2008). In this regard, other neuropeptides released into the SON have been demonstrated to cause local ischemia (Alonso et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Opposing Actions of Endothelin-1 on Glutamatergic Transmission onto Vasopressin and Oxytocin Neurons in the Supraoptic Nucleus

Zampronio¹,

Kuzmiski²,

Florence³

et al. 2010

J. Neurosci.

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Endothelin (ET-1) given centrally has many reported actions on hormonal and autonomic outputs from the CNS. However, it is unclear whether these effects are due to local ischemia via its vasoconstrictor properties or to a direct neuromodulatory action. ET-1 stimulates the release of oxytocin (OT) and vasopressin (VP) from supraoptic magnocellular (MNCs) neurons in vivo; therefore, we asked whether ET-1 modulates the excitatory inputs onto MNCs that are critical in sculpting the activity of these neurons. To investigate whether ET-1 modulates excitatory synaptic transmission, we obtained whole-cell recordings and analyzed quantal glutamate release onto MNCs in the supraoptic nucleus (SON). Neurons identified as VP-containing neurosecretory cells displayed a decrease in quantal frequency in response to ET-1 (10 -100 pM). This decrease was mediated by ET A receptor activation and production of a retrograde messenger that targets presynaptic cannabinoid-1 receptors. In contrast, neurons identified as OT-containing MNCs displayed a transient increase in quantal glutamate release in response to ET-1 application via ET B receptor activation. Application of TTX to block action potentialdependent glutamate release inhibited the excitatory action of ET-1 in OT neurons. There were no changes in quantal amplitude in either MNC type, suggesting that the effects of ET-1 were via presynaptic mechanisms. A gliotransmitter does not appear to be involved as ET-1 failed to elevate astrocytic calcium in the SON. Our results demonstrate that ET-1 differentially modulates glutamate release onto VPversus OT-containing MNCs, thus implicating it in the selective regulation of neuroendocrine output from the SON.

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Section: Introductionmentioning

confidence: 99%

Opposing Actions of Endothelin-1 on Glutamatergic Transmission onto Vasopressin and Oxytocin Neurons in the Supraoptic Nucleus

Zampronio¹,

Kuzmiski²,

Florence³

et al. 2010

J. Neurosci.

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“…ET-1 induces excitation of neurons in the spinal cord and trigeminal system (44,45) . These findings suggest roles for ETs in neurotransmission, which Dashwood and Loesch recently presented a detailed review (46) . Increases in brain ETs are observed in nerve injury animal models (47,48) .…”

Section: The Et System In the Central Nervous System Et Production Inmentioning

confidence: 74%

Endothelin systems in the brain: involvement in pathophysiological responses of damaged nerve tissues

Kōyama

2013

BioMolecular Concepts

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In addition to their potent vasoconstriction effects, endothelins (ETs) show multiple actions in various tissues including the brain. The brain contains high levels of ETs, and their production is stimulated in many brain disorders. Accumulating evidence indicates that activation of brain ET receptors is involved in several pathophysiological responses in damaged brains. In this article, the roles of brain ET systems in relation to brain disorders are reviewed. In the acute phase of stroke, prolonged vasospasm of cerebral arteries and brain edema occur, both of which aggravate brain damage. Studies using ET antagonists show that activation of ETA receptors in the brain vascular smooth muscle induces vasospasm after stroke. Brain edema is induced by increased activity of vascular permeability factors, such as vascular endothelial growth factor and matrix metalloproteinases. Activation of ETB receptors stimulates astrocytic production of these permeability factors. Increases in reactive astrocytes are observed in neurodegenerative diseases and in the chronic phase of stroke, where they facilitate the repair of damaged nerve tissues by releasing neurotrophic factors. ETs promote the induction of reactive astrocytes through ETB receptors. ETs also stimulate the production of astrocytic neurotrophic factors. Recent studies have shown high expression of ETB receptors in neural progenitors. Activation of ETB receptors in neural progenitors promotes their proliferation and migration, suggesting roles for ETB receptors in neurogenesis. Much effort has been invested in the pursuit of novel drugs to induce protection or repair of damaged nerve tissues. From these studies, the pharmacological significance of brain ET systems as a possible target of neuroprotective drugs is anticipated.

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“…It has also been demonstrated that in cerebral blood vessels ET-1 is released and acts from the abluminal (adventitial) and not from the endoluminal side. Endothelin-1 accounts for the majority of pathobiological effects exerted by endothelins, including the above-mentioned neurological pathologies [4][5][6][7][8][9][10]. In most of the tissues endothelins are primarily produced by endothelium, but in human brain the astrocytes are the main source of ET-1, especially in the settings of neuroischaemic disorders.…”

Section: Endothelin-1 Concentrations In Peripheral Jugular and Azygmentioning

confidence: 99%

Endothelin-1 concentrations in the internal jugular and azygous veins in multiple sclerosis patients: the results of a pilot study

Simka¹,

Ludyga²,

Janas³

et al. 2014

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Objectives: In this pilot study we examined the potent vasoconstrictor, endothelin-1, in the blood of multiple sclerosis patients in the context of chronic cerebrospinal venous insufficiency hypothesis. For this purpose we measured endothelin-1 concentrations in blood samples that were obtained during selective catheterisation of the main veins draining the central nervous system: the internal jugular veins and the azygous vein. Material and methods:We measured endothelin-1 concentrations in peripheral blood in nine multiple sclerosis patients and five healthy controls. In multiple sclerosis patients this peptide was also evaluated in blood samples obtained from the internal jugular veins and azygous vein. Also, in five patients peripheral endothelin-1 levels were measured one and seven days after angioplasty for stenosed internal jugular veins. Results: We found similar concentrations of endothelin-1 in peripheral blood in multiple sclerosis patients and healthy controls, a higher endothelin-1 level in the upper part of right internal jugular veins, and unchanged concentrations of this peptide in peripheral blood following angioplasty. Conclusions: Considering the pilot nature of our trial and the small number of the patients and controls assessed, our findings should be interpreted with caution, but they may represent a useful framework for further research in this field. However, our study shows that it is unlikely that endothelin-1 circulating in the blood is responsible for the symptoms of multiple sclerosis.

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Endothelin‐1 as a neuropeptide: neurotransmitter or neurovascular effects?

Cited by 41 publications

References 123 publications

Opposing Actions of Endothelin-1 on Glutamatergic Transmission onto Vasopressin and Oxytocin Neurons in the Supraoptic Nucleus

Opposing Actions of Endothelin-1 on Glutamatergic Transmission onto Vasopressin and Oxytocin Neurons in the Supraoptic Nucleus

Endothelin systems in the brain: involvement in pathophysiological responses of damaged nerve tissues

Endothelin-1 concentrations in the internal jugular and azygous veins in multiple sclerosis patients: the results of a pilot study

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