Current Issue

Effect of GLP-1 on MNCs activity in hypothalamic paraventricular nucleus in vitro in rats

JIN Xin¹, CHEN Li^2,3, CHU Chun-Ping², LI Yu-Zi¹, REN Peng⁴, QIU De-Lai^2,*

¹Department of Cardiology, Yanbian University Hospital, Yanji 133000, China；²Brain Science Institute, Jilin Medical University, Jilin 132013, China；³Department of Physiology and Pathophysiology, College of Medicine, Yanbian University, Yanji 133002, China；⁴College of Physical Education, Yuxi Normal University, Yuxi 653100, China

Abstract

Glucagon-like peptide-1 (GLP-1) in the brain is synthesized by preproglucagon neurons and released through axonal projections to extensive regions such as the arcuate nucleus, hypothalamic paraventricular nucleus (PVN), rostral ventrolateral medulla, and dorsomedial medulla. It is involved in functional activities including substance metabolism, neuroendocrine regulation, and autonomic nerve control. The GLP-1 receptor (GLP-1R) is highly expressed in the PVN and plays an important role in stress responses and cardiovascular activities. However, the mechanism by which GLP-1 influences the activity of magnocellular neurosecretory cells (MNCs) in the hypothalamic PVN remains unclear. In this study, we used whole-cell patch-clamp recording in acute hypothalamic slices, biotin staining, double immunofluorescence staining, and neuropharmacology methods to investigate the regulatory mechanism of GLP-1 on the activity of the hypothalamic PVN MNCs in vitro in rats. Under current-clamp conditions, perfusion with GLP-1 (100 nmol/L) resulted in a significant decrease in the spontaneous firing frequency of PVN MNCs accompanied with a membrane potential hyperpolarization. Blocking ionotropic glutamate receptors and GABAA receptors either alone or simultaneously did not affect the inhibitory effect of GLP-1 on the firing frequency of PVN MNCs. GLP-1 had no significant impact on the half-width, rise constant, or decay constant of action potentials, but it significantly increased the after-hyperpolarization (AHP) and inwardly rectifying potassium currents of PVN MNCs. The results of double immunofluorescence showed that GLP-1 significantly reduced the expression of c-fos in arginine vasopressin (AVP)-ergic neurons. These results indicate that GLP-1 activates postsynaptic inwardly rectifying potassium channels, reduces the excitability of PVN MNCs, and decreases their firing frequency and c-fos expression. These findings suggest that GLP-1 reduces the secretion and release of AVP by inhibiting the functional activity of PVN MNCs in rats.

Key words: glucagon-like peptide-1; brain slice patch-clamp recording; hypothalamic paraventricular nucleus; magnocellular neurosecretory cells; inwardly rectifying potassium currents

Received: 　　Accepted:

Corresponding author: 邱德来　　E-mail:

DOI: 10.13294/j.aps.2026.0042

Citing This Article：

JIN Xin, CHEN Li, CHU Chun-Ping, LI Yu-Zi, REN Peng, QIU De-Lai. Effect of GLP-1 on MNCs activity in hypothalamic paraventricular nucleus in vitro in rats. Acta Physiol Sin 2026; 78 (3): 642-652 (in Chinese with English abstract).