The paraventricular hypothalamic nucleus is involved in exendin-4-induced emesis and inhibition of food and water intake in Suncus murinus
Author(s)
Author(s)
Cui, D.
Liu, J. Y. H.
Ngan, M. P.
Rudd, J. A.
Date Issued
2021
Publisher
John Wiley & Sons
Journal
United European Gastroenterology Journal
Volume
9
Issue
S8
Start page
278
End page
278
Abstract
Introduction
Our previous studies using Suncus murinus demonstrated that the action of exendin-4 to induce emesis is mediated via GLP-1 receptors in the brainstem and/or hypothalamus; its anorectic action may involve similar brain areas and a “non-classical” GLP-1 receptor. Aims & Methods In the present studies, we investigated if the emetic and anorectic effects of exendin-4 involve the paraventricular hypothalamic nucleus. The expression of GLP-1 immunoreactive neurons and GLP-1 receptors were measured using immunohistochemistry. In functional studies, animals were anaesthetized with sodium pentobarbitone (40 mg/kg, i.p.) and then stereotaxically implanted with a guide cannula into the paraventricular hypothalamic nuclei and allowed a 7-days recovery before further experimentation. Animals were fasted 12 h prior to administration of exendin-4 (3 – 300 pmol, iPVH) or saline (1 µl, iPVH). Food and water consumption and behavior were measured for 1 hour. Results GLP-1 immunoreactive neurons and receptors were detected in the paraventricular hypothalamic nucleus of S. murinus. In conscious, freely moving animals, iPVH administration of exendin-4 (3 – 30 pmol) inhibited significantly food and water intake in a dose-dependent manner (P <0.05; n = 4 – 6) without affecting the latency to feeding. Exendin-4 at 100 and 300 pmol, iPVH, induced emesis with 14.3 ± 3.7 and 23.3 ± 11.4 episodes, respectively, in all animals; the latency to the first episode varied between 4.1 and 83.5 min (P> 0.05). Exendin-4 at 100 and 300 pmol, iPVH, also prohibited food and water intake (P< 0.001). Conclusion Our data suggests that the paraventricular hypothalamic nucleus mediates exendin-4-induced emesis and an inhibition of food and water intake in S. murinus. These studies were fully supported by a grant from the Research Grants Council of the Hong Kong SAR, China (Project no. UGC/FDS11/M02/15).
Our previous studies using Suncus murinus demonstrated that the action of exendin-4 to induce emesis is mediated via GLP-1 receptors in the brainstem and/or hypothalamus; its anorectic action may involve similar brain areas and a “non-classical” GLP-1 receptor. Aims & Methods In the present studies, we investigated if the emetic and anorectic effects of exendin-4 involve the paraventricular hypothalamic nucleus. The expression of GLP-1 immunoreactive neurons and GLP-1 receptors were measured using immunohistochemistry. In functional studies, animals were anaesthetized with sodium pentobarbitone (40 mg/kg, i.p.) and then stereotaxically implanted with a guide cannula into the paraventricular hypothalamic nuclei and allowed a 7-days recovery before further experimentation. Animals were fasted 12 h prior to administration of exendin-4 (3 – 300 pmol, iPVH) or saline (1 µl, iPVH). Food and water consumption and behavior were measured for 1 hour. Results GLP-1 immunoreactive neurons and receptors were detected in the paraventricular hypothalamic nucleus of S. murinus. In conscious, freely moving animals, iPVH administration of exendin-4 (3 – 30 pmol) inhibited significantly food and water intake in a dose-dependent manner (P <0.05; n = 4 – 6) without affecting the latency to feeding. Exendin-4 at 100 and 300 pmol, iPVH, induced emesis with 14.3 ± 3.7 and 23.3 ± 11.4 episodes, respectively, in all animals; the latency to the first episode varied between 4.1 and 83.5 min (P> 0.05). Exendin-4 at 100 and 300 pmol, iPVH, also prohibited food and water intake (P< 0.001). Conclusion Our data suggests that the paraventricular hypothalamic nucleus mediates exendin-4-induced emesis and an inhibition of food and water intake in S. murinus. These studies were fully supported by a grant from the Research Grants Council of the Hong Kong SAR, China (Project no. UGC/FDS11/M02/15).
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