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 microM 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 microM alpha-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 4 alpha-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.
Manzoni
O J
OJ
Centre CNRS-INSERM de Pharmacologie-Endocrinologie, Montpellier, France.
Finiels-Marlier
F
F
Sassetti
I
I
Blockaert
J
J
le Peuch
C
C
Sladeczek
F A
FA
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003600:Cytosol / Q000201:enzymology; D007051:Ibotenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism* / Q000502:physiology; D018091:Receptors, AMPA; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*; D019311:Staurosporine; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D000470:Alkaloids; D018091:Receptors, AMPA; D017981:Receptors, Neurotransmitter; D007051:Ibotenic Acid; D015240:Phorbol 12,13-Dibutyrate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D011493:Protein Kinase C; D019311:Staurosporine