METABOTROPIC GLUTAMATE-RECEPTOR SUBTYPE 1A ACTIVATES ADENYLATE-CYCLASE WHEN EXPRESSED IN BABY HAMSTER-KIDNEY CELLS

1. The coupling of subtype mGluR1a of the metabotropic glutamate recep tor family to phosphoinositide hydrolysis, cAMP-formation and arachido nic acid release was characterized when the receptor was expressed in baby hamster kidney (BHK) cells. 2. When measuring cAMP-formation in B HK cells expressing mGluR1a, the rank order of agonist potency as well as the efficacy of mGluR1a antagonists was comparable to what has bee n observed when measuring mGluR1a-mediated phosphoinositide (PI)-hydro lysis. 3. However, while the presence of extracellular calcium increas ed the efficacy of quisqualate to stimulate phosphoinositide hydrolysi s no significant effects were observed when measuring quisqualate-indu ced cAMP-formation. 4. Pretreatment of mGluR1a-expressing cells with p ertussis toxin increased quisqualate-induced cAMP-formation in contras t to the observed partial inhibition of PI-hydrolysis by pertussis tox in. Cholera toxin increased cAMP-formation in BHK cells but showed no effects on PI-hydrolysis. 5. While quisqualate also stimulated [H-3]-a rachidonic acid release from BHK cells expressing mGluR1a this effect may be secondary to activation of phospholipase C. 6. These data furth er suggest that mGluR1a is coupled to PI-hydrolysis as well as cAMP-fo rmation via different G-proteins which can be discriminated by their s ensitivity to pertussis toxin.