A novel mechanism of neurokinin-1 receptor resensitization.

Title

A novel mechanism of neurokinin-1 receptor resensitization.

Creator

Bennett V J; Perrine S A; Simmons M A

Publisher

The Journal of pharmacology and experimental therapeutics

Date

2002
2002-12

Description

Prolonged or repeated activation of many G protein-coupled receptors induces rapid desensitization followed by a period during which receptors are resensitized. In this study, concanavalin A (Con A) and monensin were used to investigate the mechanisms of desensitization and resensitization of the neurokinin-1 receptor. Con A inhibits internalization, whereas monensin prevents receptor recycling. The effects of Con A and monensin on desensitization, resensitization, receptor phosphorylation, endocytosis, and recycling of the neurokinin-1 receptor were assessed. Desensitization was defined as the decrease in the ability of substance P (SP) to elicit an intracellular Ca2+ response after a prolonged SP exposure. Resensitization was characterized as the return of SP responsiveness. Under control conditions, desensitization occurred after a 5-min exposure to agonist. Resensitization was evident 30 min after agonist washout. Neither monensin nor Con A prevented desensitization. Monensin completely inhibited resensitization, whereas Con A decreased but did not completely block resensitization. Receptor phosphorylation was increased after agonist activation and returned to basal levels after a recovery period. Neither Con A nor monensin altered the amount of agonist-specific receptor phosphorylation. Receptor binding analysis showed that plasma membrane receptors were internalized after a 5-min agonist exposure. Receptor recycling was not observed after a 1-h recovery period; however, resensitization was apparent. Taken together, these results suggest that rapid neurokinin-1 receptor desensitization can occur without receptor internalization and that resensitization occurs before receptor recycling.

Subject

Animals; Cell Membrane/drug effects/metabolism; CHO Cells; Concanavalin A/pharmacology; Cricetinae; Monensin/pharmacology; Neurokinin-1/*agonists/*metabolism; Phosphorylation/drug effects; Rats; Receptors

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

1155–1162

Issue

3

Volume

303

Citation

Bennett V J; Perrine S A; Simmons M A, “A novel mechanism of neurokinin-1 receptor resensitization.,” NEOMED Bibliography Database, accessed April 15, 2021, https://neomed.omeka.net/items/show/4522.

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