Complex Involvement of Pertussis Toxin-Sensitive G Proteins in the Regulation of Type 1a Metabotropic Glutamate Receptor Signaling in Baby Hamster Kidney Cells

Previously, we demonstrated that the coupling of the metabo-tropic glutamate receptor mGlu1a to phosphoinositide hydro-lysis is enhanced by pertussis toxin (PTX) in stably transfected baby hamster kidney cells (BHK). Here, we show that the PTX effect on agonist-stimulated [3H]inositol phosphate accumula-tion can be resolved into two components: an immediate in-crease in agonist potency, and a more slowly developing in-crease in the magnitude of the response observed at maximally effective agonist concentrations. Using Gq/11a- and Gi/oa-se-lective antibodies to immunoprecipitate [35S]guanosine-59-O-(3-thio)triphosphate-bound Ga proteins, we also show that ag-onist stimulation of mGlu1a in BHK membranes increases specific [35S]guanosine-59-O-(3-thio)triphosphate binding to both Gq/11 and Gi/o proteins. Preincubation of BHK-mGlu1