Type:

Other

Description:

G protein–coupled receptors (GPCRs) traverse the plasma membrane seven times and produce intracellular effects through interaction with G proteins. Three classes of ligands bind and regulate the activity of GPCRs: agonists, antagonists, and inverse agonists. To describe the activity of these ligands at GPCRs, a two-state receptor model has been proposed in which receptors exist in an equilibrium between inactive (R) and active (R*) states. Agonists preferentially bind and stabilize the active (R*) state. This results in an enrichment of the proportion of active receptors, producing an increase in receptor activity. In contrast, inverse agonists preferentially bind and stabilize receptors in the inactive (R) state. This results in an enrichment of the proportion of inactive receptors, producing a reduction in spontaneous receptor activity. Neutral antagonists have equal preferences for both R and R* states, lack any intrinsic activity, and are able to block actions produced by either agonists or inverse agonists. Exciting observations reported in two recent manuscripts by Gbahou et al. and Azzi et al. indicate that some inverse agonists act not only in opposition to agonists by suppressing constitutive receptor activity, but may also initiate unique signal transduction cascades as well. Specifically, it is proposed that these unique ligands are able to enrich several distinct active receptor conformations, each demonstrating a preference for regulation of a discrete intracellular effector. This suggests that inverse agonists are not merely "the opposite of agonists," but instead may serve as useful tools to investigate ligand-specific conformations of GPCRs.

Subjects:

    Education Levels:

      Keywords:

      NSDL,NSDL_SetSpec_BEN,signal transduction,G proteins,GPCRs,Life Science,oai:nsdl.org:2200/20090721035831105T

      Language:

      English

      Access Privileges:

      Public - Available to anyone

      License Deed:

      Creative Commons Attribution Non-Commercial Share Alike

      Collections:

      None
      This resource has not yet been aligned.
      Curriki Rating
      'NR' - This resource has not been rated
      NR
      'NR' - This resource has not been rated

      This resource has not yet been reviewed.

      Not Rated Yet.

      Non-profit Tax ID # 203478467