G-protein-coupled receptors, GPCRs, constitute a vast protein family that encompasses a wide range of functions (including various autocrine, paracrine and endocrine processes). They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups. We use the term clan to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence [1]. The currently known clan members include the rhodopsin-like GPCRs, the secretin-like GPCRs, the cAMP receptors, the fungal mating pheromone receptors, and the metabotropic glutamate receptor family. There is a specialized database for GPCRs: http://www.gpcr.org/7tm/.

The metabotropic glutamate receptors are functionally and pharmacologically distinct from the ionotropic glutamate receptors. They are coupled to G-proteins and stimulate the inositol phosphate/Ca²⁺ intracellular signalling pathway [2, 3, 4, 5]. The amino acid sequences of the receptors contain high proportions of hydrophobic residues grouped into 7 domains, in a manner reminiscent of the rhodopsins and other receptors believed to interact with G-proteins. However, while a similar 3D framework has been proposed to account for this, there is no significant sequence identity between these and receptors of the rhodopsin-type family: the metabotropic glutamate receptors thus bear their own distinctive '7TM' signature. This 7TM signature is also shared by the calcium-sensing receptors, and GABA (gamma-amino-butyric acid) type B (GABA(B)) receptors.

At least eight sub-types of metabotropic receptor (MGR1-8) have been identified in cloning studies. The sub-types differ in their agonist pharmacology and signal transduction pathways [6].

MGR6 is restrictedly expressed in retinal ON bipolar cells and, on the basis of its agonist selectivity, may have a key physiological role in certain inherited eye diseases [7, 8].