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Rapid agonist-induced decrease of neurotensin receptors from the cell surface in rat cultured neurons
M A Vanisberg1, J M Maloteaux, J N Octave
1Laboratoire de Neurochimie, Université Catholique de Louvain, Brussels, Belgium.
Biochemical Pharmacology
|November 27, 1991
Summary
Neurotensin receptors on neuronal cells rapidly decrease upon agonist stimulation, indicating internalization. This process involves receptor-mediated endocytosis of neurotensin, crucial for receptor regulation.
Area of Science:
- Neuroscience
- Cell Biology
- Pharmacology
Background:
- Neurotensin receptors are present in rat neuronal cultures.
- High-affinity binding sites for neurotensin were identified.
Purpose of the Study:
- To investigate the regulation of neurotensin receptors in vitro.
- To understand the mechanism of agonist-induced receptor downregulation.
Main Methods:
- Primary neuronal cultures from rat embryos were used.
- Binding assays with [3H]neurotensin were performed on intact and homogenized cells.
- Agonist-induced changes in receptor binding and ligand uptake were measured at different temperatures.
Main Results:
- Incubation with neurotensin (1-13) rapidly decreased neurotensin receptor number by 60% within 15 minutes.
- The active neurotensin fragment (8-13) induced this decrease, but the inactive fragment (1-8) did not.
- Ligand uptake kinetics mirrored receptor disappearance, suggesting receptor-mediated endocytosis.
- Endocytosed neurotensin was sequestered and not released, indicating internalization.
Conclusions:
- Agonist stimulation triggers rapid internalization of neurotensin receptors from the cell surface.
- This process involves receptor-mediated endocytosis of the neurotensin peptide.
- The findings elucidate a key mechanism in neurotensin receptor regulation.