Structural determinants in the second intracellular loop of the human cannabinoid CB1 receptor mediate selective coupling to G(s) and G(i).

ABSTRACT:

Background and purpose

The cannabinoid CB(1) receptor is primarily thought to be functionally coupled to the G(i) form of G proteins, through which it negatively regulates cAMP accumulation. Here, we investigated the dual coupling properties of CB(1) receptors and characterized the structural determinants that mediate selective coupling to G(s) and G(i).

Experimental approach

A cAMP-response element reporter gene system was employed to quantitatively analyze cAMP change. CB(1)/CB(2) receptor chimeras and site-directed mutagenesis combined with functional assays and computer modelling were used to determine the structural determinants mediating selective coupling to G(s) and G(i).

Key results

CB(1) receptors could couple to both G(s)-mediated cAMP accumulation and G(i)

SUBMITTER: Chen XP 

PROVIDER: S-EPMC3010585 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature