Vagally mediated gastric effects of brain stem α 2 -adrenoceptor activation in stressed rats

Yanyan Jiang, Kirsteen Browning, Luca Toti, Renato Alberto Travagli

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6 Citations (Scopus)

Abstract

Chronic stress exerts vagally dependent effects to disrupt gastric motility; previous studies have shown that, among other nuclei, A2 neurons are involved in mediating these effects. Several studies have also shown robust in vitro and in vivo effects of α2-adrenoceptor agonists on vagal motoneurons. We have demonstrated previously that brainstem vagal neurocircuits undergo remodeling following acute stress; however, the effects following brief periods of chronic stress have not been investigated. Our aim, therefore, was to test the hypothesis that different types of chronic stress influence gastric tone and motility by inducing plasticity in the response of vagal neurocircuits to α 2 -adrenoreceptor agonists. In rats that underwent 5 days of either homotypic or heterotypic stress loading, we applied the α 2 -adrenoceptor agonist, UK14304, either by in vitro brainstem perfusion to examine its ability to modulate GABAergic synaptic inputs to vagal motoneurons or in vivo brainstem microinjection to observe actions to modulate antral tone and motility. In neurons from naïve rats, GABAergic currents were unresponsive to exogenous application of UK14304. In contrast, GABAergic currents were inhibited by UK14304 in all neurons from homotypic and, in a subpopulation of neurons, heterotypic stressed rats. In control rats, UK14304 microinjection inhibited gastric tone and motility via withdrawal of vagal cholinergic tone; in heterotypic stressed rats, the larger inhibition of antrum tone was due to a concomitant activation of peripheral nonadrenergic, noncholinergic pathways. These data suggest that stress induces plasticity in brainstem vagal neurocircuits, leading to an upregulation of α 2 -mediated responses. NEW & NOTEWORTHY Catecholaminergic neurons of the A2 area play a relevant role in stress-related dysfunction of the gastric antrum. Brief periods of chronic stress load induce plastic changes in the actions of adrenoceptors on vagal brainstem neurocircuits.

Original languageEnglish (US)
Pages (from-to)G504-G516
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume314
Issue number4
DOIs
StatePublished - Apr 1 2018

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Adrenergic Receptors
Brain Stem
Stomach
Neurons
Microinjections
Motor Neurons
varespladib methyl
Pyloric Antrum
Cholinergic Agents
Up-Regulation
Perfusion
In Vitro Techniques

All Science Journal Classification (ASJC) codes

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

Cite this

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title = "Vagally mediated gastric effects of brain stem α 2 -adrenoceptor activation in stressed rats",
abstract = "Chronic stress exerts vagally dependent effects to disrupt gastric motility; previous studies have shown that, among other nuclei, A2 neurons are involved in mediating these effects. Several studies have also shown robust in vitro and in vivo effects of α2-adrenoceptor agonists on vagal motoneurons. We have demonstrated previously that brainstem vagal neurocircuits undergo remodeling following acute stress; however, the effects following brief periods of chronic stress have not been investigated. Our aim, therefore, was to test the hypothesis that different types of chronic stress influence gastric tone and motility by inducing plasticity in the response of vagal neurocircuits to α 2 -adrenoreceptor agonists. In rats that underwent 5 days of either homotypic or heterotypic stress loading, we applied the α 2 -adrenoceptor agonist, UK14304, either by in vitro brainstem perfusion to examine its ability to modulate GABAergic synaptic inputs to vagal motoneurons or in vivo brainstem microinjection to observe actions to modulate antral tone and motility. In neurons from na{\"i}ve rats, GABAergic currents were unresponsive to exogenous application of UK14304. In contrast, GABAergic currents were inhibited by UK14304 in all neurons from homotypic and, in a subpopulation of neurons, heterotypic stressed rats. In control rats, UK14304 microinjection inhibited gastric tone and motility via withdrawal of vagal cholinergic tone; in heterotypic stressed rats, the larger inhibition of antrum tone was due to a concomitant activation of peripheral nonadrenergic, noncholinergic pathways. These data suggest that stress induces plasticity in brainstem vagal neurocircuits, leading to an upregulation of α 2 -mediated responses. NEW & NOTEWORTHY Catecholaminergic neurons of the A2 area play a relevant role in stress-related dysfunction of the gastric antrum. Brief periods of chronic stress load induce plastic changes in the actions of adrenoceptors on vagal brainstem neurocircuits.",
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AU - Jiang, Yanyan

AU - Browning, Kirsteen

AU - Toti, Luca

AU - Travagli, Renato Alberto

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N2 - Chronic stress exerts vagally dependent effects to disrupt gastric motility; previous studies have shown that, among other nuclei, A2 neurons are involved in mediating these effects. Several studies have also shown robust in vitro and in vivo effects of α2-adrenoceptor agonists on vagal motoneurons. We have demonstrated previously that brainstem vagal neurocircuits undergo remodeling following acute stress; however, the effects following brief periods of chronic stress have not been investigated. Our aim, therefore, was to test the hypothesis that different types of chronic stress influence gastric tone and motility by inducing plasticity in the response of vagal neurocircuits to α 2 -adrenoreceptor agonists. In rats that underwent 5 days of either homotypic or heterotypic stress loading, we applied the α 2 -adrenoceptor agonist, UK14304, either by in vitro brainstem perfusion to examine its ability to modulate GABAergic synaptic inputs to vagal motoneurons or in vivo brainstem microinjection to observe actions to modulate antral tone and motility. In neurons from naïve rats, GABAergic currents were unresponsive to exogenous application of UK14304. In contrast, GABAergic currents were inhibited by UK14304 in all neurons from homotypic and, in a subpopulation of neurons, heterotypic stressed rats. In control rats, UK14304 microinjection inhibited gastric tone and motility via withdrawal of vagal cholinergic tone; in heterotypic stressed rats, the larger inhibition of antrum tone was due to a concomitant activation of peripheral nonadrenergic, noncholinergic pathways. These data suggest that stress induces plasticity in brainstem vagal neurocircuits, leading to an upregulation of α 2 -mediated responses. NEW & NOTEWORTHY Catecholaminergic neurons of the A2 area play a relevant role in stress-related dysfunction of the gastric antrum. Brief periods of chronic stress load induce plastic changes in the actions of adrenoceptors on vagal brainstem neurocircuits.

AB - Chronic stress exerts vagally dependent effects to disrupt gastric motility; previous studies have shown that, among other nuclei, A2 neurons are involved in mediating these effects. Several studies have also shown robust in vitro and in vivo effects of α2-adrenoceptor agonists on vagal motoneurons. We have demonstrated previously that brainstem vagal neurocircuits undergo remodeling following acute stress; however, the effects following brief periods of chronic stress have not been investigated. Our aim, therefore, was to test the hypothesis that different types of chronic stress influence gastric tone and motility by inducing plasticity in the response of vagal neurocircuits to α 2 -adrenoreceptor agonists. In rats that underwent 5 days of either homotypic or heterotypic stress loading, we applied the α 2 -adrenoceptor agonist, UK14304, either by in vitro brainstem perfusion to examine its ability to modulate GABAergic synaptic inputs to vagal motoneurons or in vivo brainstem microinjection to observe actions to modulate antral tone and motility. In neurons from naïve rats, GABAergic currents were unresponsive to exogenous application of UK14304. In contrast, GABAergic currents were inhibited by UK14304 in all neurons from homotypic and, in a subpopulation of neurons, heterotypic stressed rats. In control rats, UK14304 microinjection inhibited gastric tone and motility via withdrawal of vagal cholinergic tone; in heterotypic stressed rats, the larger inhibition of antrum tone was due to a concomitant activation of peripheral nonadrenergic, noncholinergic pathways. These data suggest that stress induces plasticity in brainstem vagal neurocircuits, leading to an upregulation of α 2 -mediated responses. NEW & NOTEWORTHY Catecholaminergic neurons of the A2 area play a relevant role in stress-related dysfunction of the gastric antrum. Brief periods of chronic stress load induce plastic changes in the actions of adrenoceptors on vagal brainstem neurocircuits.

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