ent increase in phosphorylation of specific endogenous proteins.These phosphoproteins may be involved the regulation certain calcium-dependent nerve terminal functions such as neurotransmitter synthesis and release.

Dopamine, apomorphine, isoproterenol, and norepinephrine each increased the concentration of adenosine 3',5'-monophosphate in slice rat caudate nucleus. The concentrations dopamine, apomorphine causing half-maximal increases were 60, 150, 0.03 30 micromoles per liter, respectively. effect dopamine was blocked by fluphenazine, a receptor antagonist, but not propranolol, beta-andrenergic antagonist. Conversely, isoproterenol propranolol fluphenazine. results suggest that nucleus there are two...

Abstract: The dopamine (DA) uptake system in mammalian nerve terminals was studied by measuring the unidirectional influx of tritiated DA into synaptosomes prepared from rat caudate nucleus. Two distinct time‐dependent components were observed. principal component saturable with respect to concentration, required both external Na and Cl, competitively blocked micromolar concentrations psychotropic agents cocaine, benztropine, nomifensine, amphetamine, methamphetamine. This has properties...

Regulation of Na+ channels by neurotoxins has been studied in pinched-off nerve endings (synaptosomes) from rat brain. Activation the steroid batrachotoxin and alkaloid veratridine resulted an increase rate influx 22Na into synaptosomes. In presence 145 mM Na+, these agents also depolarized synaptosomes, as indicated increased fluorescence a voltage-sensitive oxacarbocyanine dye [diO-C5(3)]. Polypeptide scorpion Leiurus quinquestriatus sea anemone Anthopleura xanthogrammica potentiated...

Spatial memory was assessed in the segmental trisomic 16 mouse (Ts65Dn), a potential model for Down syndrome (DS), using 12-arm radial maze (RAM). Ts65Dn mice have portion of chromosome syntenic to distal end human 21 triplicated. On each 8 daily trials RAM, made fewer correct choices than control and performed at or near chance levels, indicating deficit spatial working memory. 9 10, as well on initial 12 choices, but required greater number complete RAM. The improved performance 10 lost...

We have identified two exons of the type III rat brain sodium channel alpha subunit gene that undergo mutually exclusive alternative RNA splicing to produce mRNAs coding either for an isoform predominant in neonatal (IIIN) or a different (IIIA) adult. These are 92 base pairs length and encode amino acids 203-232, which correspond part S3 most S4 transmembrane segments within domain I extracellular loop between them. Despite 21 nucleotide differences exons, only single acid at position 209 is...

Two nonhomologous polypeptide toxins, tityustoxin K alpha (TsTX-K alpha) and beta beta), purified from the venom of Brazilian scorpion Tityus serrulatus, selectively block voltage-gated noninactivating K+ channels in synaptosomes (IC50 values 8 nM 30 nM, respectively). In contrast, alpha-dendrotoxin (alpha-DTX) charybdotoxin (ChTX) inactivating 90 40 We studied interactions among these toxins 125I-alpha-DTX binding 86Rb efflux experiments. Both TsTX-K ChTX completely displaced specifically...

Venom from the green mamba (Dendroaspis angusticeps) blocked 86Rb efflux through voltage-gated K channels in rat brain synaptosomes. Crude venom inhibited both rapidly inactivating, 4-aminopyridine-sensitive channels, and noninactivating, phencyclidine-sensitive, channels. Fractionation of by size exclusion chromatography cation exchange high performance liquid yielded four 7000-dalton polypeptides (designated alpha-, beta-, gamma-, delta-DaTX) that synaptosome Two these toxins, alpha-...

The voltage-dependent gating of single, batrachotoxin-activated Na channels from rat brain was studied in planar lipid bilayers composed negatively charged or neutral phospholipids. relationship between the probability finding channel open state and membrane potential (Po vs. Vm) determined symmetrical NaCl, both absence free Ca2+ after addition to extracellular side channel, intracellular side, both. In Ca2+, neither midpoint (V0.5) Po Vm relation, nor steepness curve, affected by charge on...

Development of the neocortex trisomy 16 (Ts16) mouse, an animal model Down syndrome (DS), is characterized by a transient delay in radial expansion cortical wall and persistent reduction volume. Here we show that at each cell cycle during neuronogenesis, smaller proportion Ts16 progenitors exit than do control, euploid progenitors. In addition, duration was found to be longer progenitors, growth fraction reduced, increase apoptosis observed both proliferative postmitotic zones developing...

Mechanisms that regulate the amount of releasable Ca2+ in intracellular stores cultured mouse astrocytes were investigated using digital imaging fura-2 loaded cells. At rest, cytoplasmic concentration, [Ca2+]cyt, was about 110 nM. In absence extracellular Ca2+, cyclopiazonic acid (CPA), an inhibitor endoplasmic reticulum (ER) Ca2+-ATPase, induced a transient, four-fold increase [Ca2+]cyt due to release from inositol triphosphate (IP3) sensitive stores. Caffeine (CAF), which releases...

The survival of cultured mouse hippocampal neurons was found to be greatly enhanced by micromolar concentrations the excitatory neurotransmitter glutamate. Blockade kainate/AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) glutamate receptors increased rate neuron death, suggesting that endogenous in cultures promotes survival. Addition (0.5-1 microM) further survival, whereas excess 20 microM resulted death. Thus, vs. dose-response relation is bell-shaped with an optimal...

We have studied abnormalities in the tangential and radial expansion of cerebral cortex during fetal development trisomy 16 (Ts16) mouse, a model for human 21 (Down syndrome). Slowed neuroepithelium Ts16 resulted reduction final telencephalic size is predicted to decrease number cortical units mature brain. In addition, growth was delayed at time peak neurogenesis normal mice, but by embryonic day 18 reached thickness. Because mouse chromosome shares many genes with 21, brain may parallel 21.