Cockroach GABA_B receptor subtypes: Molecular characterization, pharmacological properties and tissue distribution

γ-aminobutyric acid (GABA) is the predominant inhibitory neurotransmitter in the central nervous system (CNS). Its effects are mediated by either ionotropic GABA_A receptors or metabotropic GABA_B receptors. GABA_B receptors regulate, via G_i/o G-proteins, ion channels, and adenylyl cyclases. In humans, GABA_B receptor subtypes are involved in the etiology of neurologic and psychiatric disorders. In arthropods, however, these members of the G-protein-coupled receptor family are only inadequately characterized. Interestingly, physiological data have revealed important functions of GABA_B receptors in the American cockroach, Periplaneta americana. We have cloned cDNAs coding for putative GABA_B receptor subtypes 1 and 2 of P. americana (PeaGB1 and PeaGB2). When both receptor proteins are co-expressed in mammalian cells, activation of the receptor heteromer with GABA leads to a dose-dependent decrease in cAMP production. The pharmacological profile differs from that of mammalian and Drosophila GABA_B receptors. Western blot analyses with polyclonal antibodies have revealed the expression of PeaGB1 and PeaGB2 in the CNS of the American cockroach. In addition to the widespread distribution in the brain, PeaGB1 is expressed in salivary glands and male accessory glands. Notably, PeaGB1-like immunoreactivity has been detected in the GABAergic salivary neuron 2, suggesting that GABA_B receptors act as autoreceptors in this neuron. This article is part of the Special Issue entitled 'GABAergic Signaling in Health and Disease'.