Enhanced cAMP Response of Naturally Occurring Mutant of Human β_3-Adrenergic Receptor

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Author(s)

Abstract

We have examined the functional significance of the naturally occurring mutation at position 64 of human β<sub>3</sub>-adrenergic receptor (β<sub>3</sub>AR), which changes the amino acid from tryptophan to arginine (W64R-β<sub>3</sub>AR). The affinities of βAR agonists for W64R-β<sub>3</sub>AR expressed in COS-7 cells were not significantly different from those for wild type β<sub>3</sub>AR. When two receptors are expressed at various expression levels, and stimulated with CGP12177A, they showed essentially the same EC<sub>50</sub> values and maximal responses. Overexpression of G<sub>i</sub> and G<sub>o</sub>, or the treatment with pertussis toxin did not affect the agonist-induced cAMP response, suggesting that G<sub>i</sub> and G<sub>o</sub> did not contribute to the β<sub>3</sub>AR-induced cAMP response. However, the enhanced cAMP response was observed when W64R-β<sub>3</sub>AR was coexpressed with the adenylyl cyclase type III isoform, and stimulated by CGP12177A and isoproterenol. These results indicate that the cAMP response of W64R-β<sub>3</sub>AR can be enhanced under the particular condition that adenylyl cyclase type III was coexpressed.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 88(3), 314-318, 2002-03-01

    The Japanese Pharmacological Society

References:  18

Cited by:  1

Codes

  • NII Article ID (NAID)
    10008187946
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    00215198
  • NDL Article ID
    6119574
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  CJPref  NDL  J-STAGE 
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