Presynaptic metabotropic glutamate and GABAB receptors

Glutamate and GABA, the two most abundant neurotransmitters in the mammalian central nervous system, can act on metabotropic receptors that are structurally quite dissimilar from those targeted by most other neurotransmitters/modulators. Accordingly, metabotropic glutamate receptors (mGluRs) and GABA(B) receptors (GABA(B)Rs) are classified as members of family 3 (or family C) of G protein-coupled receptors. On the other hand, mGluRs and GABA(B)Rs exhibit pronounced and partly unresolved differences between each other. The most intriguing difference is that mGluRs exist as multiple pharmacologically as well as structurally distinct subtypes, whereas, in the case of GABA(B)Rs, molecular biologists have so far identified only one structurally distinct heterodimeric complex whose few variants seem unable to explain the pharmacological heterogeneity of GABA(B)Rs observed in many functional studies. Both mGluRs and GABA(B)Rs can be localized on axon terminals of different neuronal systems as presynaptic autoreceptors and heteroreceptors modulating the exocytosis of various transmitters.