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Updated: Aug 9, 2026
Functional Evaluation of Biological Neurotoxins in Networked Cultures of Stem Cell-derived Central Nervous System Neurons
Published on: February 5, 2015
Sustained neurotensin exposure promotes cell surface recruitment of NTS2 receptors
Amélie Perron1, Nadder Sharif, Louis Gendron
1Montreal Neurological Institute, McGill University, Montreal, Que., Canada H3A 2B4.
Abstract:
In this study, we investigated whether persistent agonist stimulation of NTS2 receptors gives rise to down-regulation, in light of reports that their activation induced long-lasting effects. To address this issue, we incubated COS-7 cells expressing the rat NTS2 with neurotensin (NT) for up to 24 h and measured resultant cell surface [125I]-NT binding. We found that NTS2-expressing cells retained the same surface receptor density despite efficient internalization mechanisms. This preservation was neither due to NTS2 neosynthesis nor recycling since it was not blocked by cycloheximide or monensin. However, it appeared to involve translocation of spare receptors from internal stores, as NT induced NTS2 migration from trans-Golgi network to endosome-like structures. This stimulation-induced regulation of cell surface NTS2 receptors was even more striking in rat spinal cord neurons. Taken together, these results suggest that sustained NTS2 activation promotes recruitment of intracellular receptors to the cell surface, thereby preventing functional desensitization.
Insights
Persistent stimulation of neurotensin receptor 2 (NTS2) prevents desensitization by moving internal receptors to the cell surface. This mechanism maintains NTS2 receptor density during prolonged neurotensin (NT) exposure.
Area of Science:
- Neuroscience
- Cell Biology
- Pharmacology
Background:
- Neurotensin receptor 2 (NTS2) activation is known to induce long-lasting effects.
- The potential for receptor down-regulation under persistent stimulation requires investigation.
Purpose of the Study:
- To determine if persistent agonist stimulation of NTS2 receptors leads to their down-regulation.
- To elucidate the mechanisms underlying NTS2 receptor regulation during sustained neurotensin (NT) exposure.
Main Methods:
- COS-7 cells expressing rat NTS2 were incubated with neurotensin (NT) for up to 24 hours.
- Cell surface [125I]-NT binding was measured to assess receptor density.
- The effects of cycloheximide and monensin on receptor preservation were evaluated.
Main Results:
- NTS2-expressing cells maintained surface receptor density despite efficient internalization.
- Receptor preservation was independent of neosynthesis or recycling, as indicated by resistance to cycloheximide and monensin.
- Neurotensin (NT) induced NTS2 receptor translocation from the trans-Golgi network to endosome-like structures, suggesting mobilization from internal stores.
- This effect was more pronounced in rat spinal cord neurons.
Conclusions:
- Sustained NTS2 activation promotes the recruitment of intracellular receptors to the cell surface.
- This recruitment mechanism prevents functional desensitization of NTS2 receptors.
- The findings reveal a novel regulatory pathway for maintaining receptor availability during prolonged agonist stimulation.
