No abstract

Abstract— The effects of maximal electroshock (MES) and phenytoin on metabolites and cyclic nucleotides in layers of frozen‐dried cerebellum have been investigated. The four layers (molecular, Purkinje‐cell rich, granular and white matter) had remarkably homogeneous distributions of P‐creatine, ATP, glucose, glycogen, lactate, GABA and the cyclic nucleotides. MES caused dramatic decreases in P‐creatine, ATP, and glucose at 10 s after treatment, followed by a decrease in glycogen at 30 s. Lactate levels were elevated, and GABA was unchanged. Cyclic AMP concentrations were increased at 10s and cyclic GMP at 30 s. Phenytoin modified most of the MES induced changes in all the layers, although white matter was less affected by MES and/or phenytoin. Lactate concentrations were increased by MES and these effects were not altered when phenytoin was administered. The most dramatic effects of phenytoin were on the changes in cyclic nucleotides. Cyclic AMP concentrations were elevated after MES but the values returned to normal more rapidly when phenytoin was present. The drug almost obliterated the MES induced changes in cyclic GMP. The possible relationship of cyclic nucleotide concentrations and the modulation of seizure activity is discussed.

Exposure of rat C6 glioma cells to either agonists or agents that increase cyclic AMP levels leads to down-regulation of 8,-adrenergic receptors (01AR) as measured by loss of radioligand binding sites . The present study examines the influence of isoproterenol and forskolin treatment on levels of,6 1AR mRNA, mRNA stability, and gene transcription rate . Isoproterenol treatment of C6 cells altered,6 1AR mRNA levels in a biphasic manner ; i .e ., short-term exposure (30-60 min) increased by 50%, whereas longer exposure (2-6 h) decreased by 50% the levels of ,61 AR mRNA . The extent of both the up-and down-regulation was dependent on agonist concentration . Similar regulation of 6 1AR mRNA was observed in forskolin-treated cells . Pretreatment of the cells with Pseudomonas exotoxin A, a potent inhibitor of protein synthesis, completely blocked isoproterenol-and forskolin-mediated down-regulation of ,6 1AR mRNA, and