Analysis of Domain Responsible for Desensitization of β_1-Adrenergic Receptor

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Author(s)

Abstract

When the wild type β<SUB>1</SUB>-adrenergic receptor (WT-β<SUB>1</SUB>AR) was expressed in Sf9 cells, the β<SUB>1</SUB>AR-stimulated adenylyl cyclase activities were desensitized by prior treatment with isoproterenol. The extent of β<SUB>1</SUB>AR desensitization was not modified, and the onset was not promoted by the overexpression of G protein-coupled receptor kinase 2 (GRK2), GRK5 or GRK6. However, overexpression of the dominant negative mutant of GRK2 appeared to inhibit desensitization of the β<SUB>1</SUB>AR. The change of the potential protein kinase A phosphorylation site located at the intracellular third loop did not affect β<SUB>1</SUB>AR desensitization. Desensitization of the truncated mutant, in which nearly all of the serine and threonine residues from the carboxyl terminus were eliminated, was the same as that of the WT-β<SUB>1</SUB>AR. A deletion mutant that lacked serine and threonine residues of the intracellualr third loop was also desensitized by isoproterenol stimulation. Furthermore, the deletion of serine and threonine residues from both the intracellular third loop and carboxyl terminus did not affect desensitization of the β<SUB>1</SUB>AR. These results suggested that phosphorylation by endogenous GRKs in Sf9 cells contributed to desensitization of the β<SUB>1</SUB>AR and that the regions other than third intracellular loop and carboxyl terminus may be responsible for β<SUB>1</SUB>AR desensitization.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 81(1), 12-20, 1999-09

    The Japanese Pharmacological Society

References:  29

Codes

  • NII Article ID (NAID)
    10008196015
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    ART
  • ISSN
    00215198
  • NDL Article ID
    4867756
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  NDL  J-STAGE 
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