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 receptor family to phosphoinositide hydrolysis, cAMP-formation and arachidonic acid release was characterized when the receptor was expressed in baby hamster kidney (BHK) cells. 2. When measuring cAMP-formation in BHK cells expressing mGluR1a, the rank order of agonist potency as well as the efficacy of mGluR1a antagonists was comparable to what has been observed when measuring mGluR1a-mediated phosphoinositide (PI)-hydrolysis. 3. However, while the presence of extracellular calcium increased the efficacy of quisqualate to stimulate phosphoinositide hydrolysis no significant effects were observed when measuring quisqualate-induced cAMP-formation. 4. Pretreatment of mGluR1a-expressing cells with pertussis toxin increased quisqualate-induced cAMP-formation in contrast to the observed partial inhibition of PI-hydrolysis by pertussis toxin. Cholera toxin increased cAMP-formation in BHK cells but showed no effects on PI-hydrolysis. 5. While quisqualate also stimulated [3H]-arachidonic acid release from BHK cells expressing mGluR1a this effect may be secondary to activation of phospholipase C. 6. These data further suggest that mGluR1a is coupled to PI-hydrolysis as well as cAMP-formation via different G-proteins which can be discriminated by their sensitivity to pertussis toxin.