Phosphorylation and desensitization of neurokinin-1 receptor expressed in epithelial cells.


Journal Article

A rat kidney epithelial cell line expressing the rat neurokinin-1 receptor (NK-1 R) was used to investigate the relationship between receptor phosphorylation and desensitization. Substance P (SP) maximally stimulated cellular inositol 1,4,5-trisphosphate (IP3) production 14-fold within 3 s, after which cellular IP3 levels rapidly diminished to near basal levels in the continuing presence of SP. SP also caused concentration-dependent phosphorylation of the NK-1R, and this effect was blocked by a receptor antagonist. Stimulation with 100 nM SP for as little as 2 s resulted in 90% desensitization of the receptor to restimulation by SP, and near-maximal receptor phosphorylation was observed at 5 s. Receptor desensitization was not affected by agents that affect protein kinase A. Phorbol 12-myristate 13-acetate (PMA) also caused phosphorylation and desensitization of the receptor but with slower kinetics and to a lesser extent than SP. PMA- but not SP-induced NK-1 R desensitization and phosphorylation were abolished by the protein kinase C inhibitor bisindolylmaleimide 1. The concentration-response curves for SP-stimulated IP3 signaling and desensitization were similar, but the curve for NK-1R phosphorylation was shifted to the right and was steeper, suggesting that the relationship between desensitization and phosphorylation is complex. These results show that both rapid homologous and rapid heterologous NK-1R desensitizations may be mediated by receptor phosphorylation but occur via distinct mechanisms with different kinetics and efficacies.

Full Text

Cited Authors

  • Vigna, SR

Published Date

  • November 1999

Published In

Volume / Issue

  • 73 / 5

Start / End Page

  • 1925 - 1932

PubMed ID

  • 10537050

Pubmed Central ID

  • 10537050

International Standard Serial Number (ISSN)

  • 0022-3042


  • eng

Conference Location

  • England