Invertebrate gamma-aminobutyric acid receptor (RDL)

The Invertebrate gamma-aminobutyric acid receptor, most notably represented by the Resistant to dieldrin (RDL) subunit, is a ligand-gated ion channel that plays a fundamental role in inhibitory neurotransmission within the invertebrate nervous system. As a member of the Cys-loop receptor superfamily, it forms a pentameric structure that conducts chloride ions across the neuronal membrane upon binding the neurotransmitter GABA, thereby hyperpolarizing the cell and suppressing action potentials. This receptor is a premier target for various classes of insecticides and antiparasitics, including phenylpyrazoles like fipronil and the newer isoxazolines used in veterinary medicine. These compounds typically act as non-competitive antagonists, binding to an allosteric site within the chloride channel pore to prevent ion flow, which causes lethal hyperexcitation in pests. While these drugs are designed for high selectivity toward invertebrate receptors, potential cross-reactivity with vertebrate GABA-A receptors remains a safety consideration, and the widespread emergence of resistance mutations in the Rdl gene poses a significant challenge for pest management and vector-borne disease control.

Other names

RDL receptorResistant to dieldrin receptorInsect GABA receptorGABA-gated chloride channelIonotropic GABA receptoriGABAR

Non-competitive antagonism of the GABA-gated chloride channel, where the drug binds to an allosteric site within the ion pore to block chloride conductance, leading to neuronal hyperexcitation, paralysis, and death of the invertebrate.