Protein kinase C-mediated inhibition of excitatory amino acid-stimulated phosphoinositide hydrolysis in the neonatal rat hippocampus.
Stimulation of phosphoinositide hydrolysis by excitatory amino acid agonists, but not cholinoceptor or adrenoceptor agonists was greater in hippocampal tissue from neonatal rats when compared to mature rats. Ibotenate (10(?3) M) and quisqualate (10(?4) M) stimulations of phosphoinositide hydrolysis were 3 and 7 times greater, respectively, in hippocampal tissue of the 7 day neonate than in the adult (60-65 day old) rat. The possibility that protein kinase C-mediated inhibitory regulation of the excitatory amino acid receptor might not be present early in postnatal development, and thus lead to an enhanced agonist response, was investigated. Pretreatment of neonatal tissue with phorbol 12,13-dibutyrate (10(?6) M), an activator protein kinase C, inhibited stimulations by ibotenate and quisqualate by 80 and 84%, respectively. Staurosporine (10(?5) M), an inhibitor of protein kinase C, potentiated responses to both ibotenate and quisqualate in neonatal tissue, and completely reversed the inhibitory effects of phorbol 12,13-dibutyrate on both agonists. These data show that the protein kinase C isozyme(s) that mediates inhibitory feedback at excitatory amino acid receptors coupled to phosphoinositide hydrolysis is present early in postnatal development. Delayed ontogeny of protein kinase C enzyme cannot explain the enhanced stimulation of phosphoinositide hydrolysis in the neonatal rat hippocampus.
Schoepp
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Central Nervous System Research, Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, U.S.A.