Islet-Activating Protein Inhibits the β-Adrenergic Receptor Facilitation Elicited by γ-Aminobutyric Acid_B Receptors

γ-Aminobutyric acid_B (GABA_B) receptor recognition sites that inhibit cyclic AMP formation, open potassium channels, and close calcium channels are coupled to these effector systems by guanine nucleotide binding proteins (G proteins). These G proteins are ADP-ribosylated by islet-activating protein (IAP), also known as pertussis tokin. This process prevents receptor coupling to these G proteins. In slices of cerebral cortex and hippocampus from rat, stimulation of GABA_B receptors with baclofen, a receptor agonist, also potentiates the accumulation of cyclic AMP stimulated by β-adrenergic agonists. It was unknown whether those GA-BA_B receptors that potentiate the β-adrenergic response were also sensitive to IAP. IAP was injected intracerebroventric-ularly into rats to ADP-ribosylate IAP-sensitive G proteins. Four days after the IAP injection, 38% and 52% of these G proteins from cerebral cortex and hippocampus, respectively, were ADP-ribosylated by the IAP injection. In slices of both structures prepared from IAP-treated rats, the GABA_B receptor-mediated potentiation of the β-adrenergic receptor response was attenuated. Thus, many GABA_B receptor-mediated responses are coupled to IAP-sensitive G proteins.