GABA Receptor Pharmacology

Summary

There is increasing evidence for the existence of “novel” receptors for the neurotransmitter GABA that pharmacologically fall outside the currently accepted classification of two major subtypes. The GABA_A/B classification, introduced in 1981, defines GABA_A receptors as being sensitive to antagonism by bicuculline and insensitive to baclofen, while GABA_B receptors are insensitive to antagonism by bicuculline and are activated by baclofen.

GABA receptors insensitive to both bicuculline and baclofen have been described extensively in both vertebrates and invertebrates. These “novel” GABA receptors have been given a variety of designations — GABA_C, GABA_NANB (non-A, non-B), and ρ-receptors (cloned from retina). With the increasing evidence for similarities between these receptors, their subtype is most conveniently designated GABA_C in an extension of the current GABA_A/B nomenclature, though a more definitive classification of GABA receptors based on pharmacological, physiological and molecular biological considerations will emerge in due course.

GABA_C receptors may constitute a third major sub-class of GABA receptors distinct in structure and function from the now classical GABA_A and GABA_B receptors. They may represent a relatively simple form of ligand gated ion channel which are made up of homo-oligomeric subunits, in contrast to the hetero-oligomeric GABA_A receptors. The more complex GABA_A receptors may have evolved from the simpler GABA_C receptors.