The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Norepinephrine triggers glutamatergic long-term potentiation in hypothalamic paraventricular nucleus magnocellular neuroendocrine cells through postsynaptic β1-AR/PKA signaling pathway in vitro in rats

  • Jing-Ri Jin (Department of Physiology and Pathophysiology, College of Medicine, Yanbian University) ;
  • Zhao-Yi Zhang (Department of Physiology and Pathophysiology, College of Medicine, Yanbian University) ;
  • Chun-Ping Chu (Department of Physiology and Pathophysiology, College of Medicine, Yanbian University) ;
  • Yu-Zi Li (Department of Cardiology, Affiliated Hospital of Yanbian University) ;
  • De-Lai Qiu (Department of Physiology and Pathophysiology, College of Medicine, Yanbian University)
  • Received : 2024.07.03
  • Accepted : 2024.07.22
  • Published : 2024.11.01
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Abstract

Norepinephrine (NE) modulates synaptic transmission and long-term plasticity through distinct subtype adrenergic receptor (AR)-mediated-intracellular signaling cascades. However, the role of NE modulates glutamatergic long-term potentiation (LTP) in the hypothalamic paraventricular nucleus (PVN) magnocellular neuroendocrine cells (MNCs) is unclear. We here investigate the effect of NE on high frequency stimulation (HFS)-induced glutamatergic LTP in rat hypothalamic PVN MNCs in vitro, by whole-cell patch-clamp recording, biocytin staining and pharmacological methods. Delivery of HFS induced glutamatergic LTP with a decrease in N2/N1 ratio in the PVN MNCs, which was enhanced by application of NE (100 nM). HFS-induced LTP was abolished by the blockade of N-methyl-D-aspartate receptors (NMDAR) with D-APV, but it was rescued by the application of NE. NE failed to rescue HFS-induced LTP of MNCs in the presence of a selective β1-AR antagonist, CGP 20712. However, application of β1-AR agonist, dobutamine HCl rescued HFS-induced LTP of MNCs in the absence of NMDAR activity. In the absence of NMDAR activity, NE failed to rescue HFS-induced MNC LTP when protein kinase A (PKA) was inhibited by extracellular applying KT5720 or intracellular administration of PKI. These results indicate that NE activates β1-AR and triggers HFS to induce a novel glutamatergic LTP of hypothalamic PVN NMCs via the postsynaptic PKA signaling pathway in vitro in rats.

Keywords

Acknowledgement

This work was supported by the Major Projects of the Ministry of Science and Technology of China (2021ZD0202300) and the National Natural Science Foundations of China (32070986, 32171005, 82160152).

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