gamma-aminobutyric acid(B) receptors: first of the functional metabotropic heterodimers.

Activation of the metabotropic gamma-aminobutyric acid(B) (GABA(B)) receptor increases K(+) conductance and decreases Ca(2+) channel activity in neuronal membranes. Studies with a number of new GABA(B) receptor agonists and antagonists reveal that in addition to their muscle relaxant effects, agonists display analgesic activity and reduce the craving for cocaine. With regard to GABA(B) receptor antagonists, preclinical data suggest they improve cognitive performance and possess antidepressant and antiepileptic potential. With a high-affinity GABA(B) antagonist, the structural properties of the receptor were characterized through expression cloning. Moreover, it has been found that expression of a fully functional GABA(B) receptor requires coupling between two separate and distinct gene products: GABA(B) R1 and GABA(B) R2. Besides being the first example of a functional heterodiameric metabotropic receptor, the components and molecular configuration of the GABA(B) receptor suggest novel mechanisms for producing pharmacologically distinct subtypes of G protein-coupled receptors.