A novel mechanism of neurokinin-1 receptor resensitization.


A novel mechanism of neurokinin-1 receptor resensitization.


Bennett V J; Perrine S A; Simmons M A


The Journal of pharmacology and experimental therapeutics




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.


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


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Bennett V J; Perrine S A; Simmons M A, “A novel mechanism of neurokinin-1 receptor resensitization.,” NEOMED Bibliography Database, accessed February 21, 2024, https://neomed.omeka.net/items/show/4522.