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Phorbol Esters Attenuate Glutamate‐Stimulated Inositol Phospholipid Hydrolysis in Neuronal Cultures
Author(s) -
Caico P. L.,
Favit A.,
Catania M. V.,
Nicoletti F.
Publication year - 1988
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1988.tb03067.x
Subject(s) - glutamate receptor , inositol phosphate , inositol , biochemistry , phospholipid , quisqualic acid , chemistry , metabotropic glutamate receptor , stimulation , phorbol , receptor , muscarinic acetylcholine receptor , diacylglycerol kinase , agonist , metabotropic glutamate receptor 1 , metabotropic glutamate receptor 5 , biology , protein kinase c , ampa receptor , endocrinology , membrane , signal transduction
The phorbol diesters 12‐ O ‐tetradecanoyl‐phorbol‐13‐acetate (TPA) and phorbol‐12,13‐dibutyrate, but not 4–α‐phorbol‐didecanoate, inhibited the stimulation of inositol phospholipid hydrolysis by excitatory amino acids and carbamylcholine in primary cultures of cerebellar neurons. This inhibition was mimicked by the synthetic diacylglycerol 1,2‐dioleoyl‐ rac ‐glycerol (DOG) and was selective for a specific glutamate‐phosphoinositide receptor subtype (GP 2 receptor) activated by glutamate and quis‐qualate. TPA was nearly inactive in inhibiting the stimulation of inositol phospholipid hydrolysis by N ‐methyl‐d‐aspartate, a selective agonist of the GP 1 receptor. Phorbol diesters and DOG attenuated the stimulation of inositol phospholipid hydrolysis by glutamate and quisqualate also in cerebellar slices from 9–15‐day‐old rats; however, using this preparation, their action was weak and required high concentrations (> 1 μ M ). The inhibition of signal transduc‐tion by phorbol diesters was not consequent to a reduced binding of glutamate to its membrane recognition sites. In fact, TPA induced only a small increase in the K D but no change in the B max of [ 3 H]glutamate binding in cerebellar membranes. Phorbol diesters may act to inhibit specific GTP‐binding proteins or particular molecular forms of phosphoinositidase C associated with GP 2 or muscarinic cholinergic receptors.