THE GLUTAMATE RECEPTOR OF THE QP-TYPE ACTIVATES PROTEIN KINASE-C AND IS REGULATED BY PROTEIN KINASE-C

In striatal neurons in primary culture quisqualate potently stimulated the formation of inositol phosphates via a metabotropic receptor we recently termed Qp in order to distinguish it from the classical ionotropic quisqualate receptor termed Qi. Here we show that 10 μM of quisqualate activated in a rapid and transient manner protein kinase C as assessed by its translocation from the cytosolic to the membrane fraction. As 10 μM α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), the Qi specific agonist, was without effect, this translocation was most probably mediated by the Qp receptor. Phorbol 12,13-dibutyrate blocked in a dose-dependent manner the Qp receptor-induced inositol phosphate formation (IC50 = 2 ± 0.4 nM). The inactive ester 4α-phorbol-12,13-didecanoate was without effect. Very low concentrations of staurosporine completely reversed the phorbol 12,13-dibutyrate-induced blockade (IC50 = 2.2 ± 1.3 nM). It can therefore be concluded that the Qp receptor is able to activate protein kinase C and that the activity of this metabotropic receptor is regulated by protein kinase C. © 1990.