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Biomedical subjects

M Sugimori

Publications and source records attributed to M Sugimori.

At least 73 records · Page 4Linked to original sources
PubMed1989

Synthesis and antileukemic activity of (+-)-20-deoxyaminocamptothecin analogues.

The camptothecin analogues (+-)-7-ethyl-10-methoxy-20-deoxyaminocamptothecin (2) and (+-)-7-ethyl-10-hydroxy-20-deoxyaminocamptothecin.HCl (3) were synthesized from indolizine compound 4 via Friedländer condensation to construct a pentacyclic ring system, and were tested in a P388 mouse antileukemia assay. Compounds 2 and 3 were more active and less toxic than (+)-camptothecin (1), and therefore had higher therapeutic ratios.

Animals↗
PubMed1989

Phosphorylation-dependent inhibition by synapsin I of organelle movement in squid axoplasm.

Synapsin I, a neuron-specific, synaptic vesicle-associated phosphoprotein, is thought to play an important role in synaptic vesicle function. Recent microinjection studies have shown that synapsin I inhibits neurotransmitter release at the squid giant synapse and that the inhibitory effect is abolished by phosphorylation of the synapsin I molecule (Llinas et al., 1985). We have considered the possibility that synapsin I might modulate release by regulating the ability of synaptic vesicles to move to, or fuse with, the plasma membrane. Since it is not yet possible to examine these mechanisms in the intact nerve terminal, we have used video-enhanced microscopy to study synaptic vesicle mobility in axoplasm extruded from the squid giant axon. We report here that the dephosphorylated form of synapsin I inhibits organelle movement along microtubules within the interior of extruded axoplasm and that phosphorylation of synapsin I on sites 2 and 3 by calcium/calmodulin-dependent protein kinase II removes this inhibitory effect. Phosphorylation of synapsin I on site 1 by the catalytic subunit of cAMP-dependent protein kinase only partially reduces the inhibitory effect. In contrast to the inhibition of movement along microtubules seen within the interior of the axoplasm, movement along isolated microtubules protruding from the edges of the axoplasm is unaffected by dephospho-synapsin I, despite the fact that the synapsin I concentration is higher there. Thus, synapsin I does not appear to inhibit the fast axonal transport mechanism itself. Rather, these results are consistent with the possibility that dephospho-synapsin I acts by a crosslinking mechanism involving some component(s) of the cytoskeleton, such as F-actin, to create a dense network that restricts organelle movement. The relevance of the present observations to regulation of neurotransmitter release is discussed.

Animals↗
PubMed1988

Spatially resolved calcium dynamics of mammalian Purkinje cells in cerebellar slice.

Microfluorometric imaging was used to study the correlation of intracellular calcium concentration with voltage-dependent electrical activity in guinea pig cerebellar Purkinje cells. The spatiotemporal dynamics of intracellular calcium concentration are demonstrated during spontaneous and evoked activity. The results are in agreement with hypotheses of dendritic segregation of calcium conductances suggested by electrophysiological experiments. These in vitro slice fluorescence imaging methods are applicable to a wide range of problems in central nervous system biochemical and electrophysiological functions.

Animals↗
PubMed1986

Electrophysiological properties and glucose responsiveness of guinea-pig ventromedial hypothalamic neurones in vitro.

The membrane properties of neurones in the guinea-pig ventromedial hypothalamic nucleus (v.m.h.) were studied in in vitro brain slice preparations. The average resting potential was -62.9 +/- 5.4 mV (mean +/- S.D.), input resistance was 155 +/- 58 M omega, and action potential amplitude was 69.9 +/- 6.3 mV. Three types of neurone were identified. The type A neurones were characterized by a short membrane time constant (7.3 +/- 2.0 ms) and a small after-hyperpolarization (a.h.p.) (2.0 +/- 1.2 mV) with a short half decay time of 67 +/- 55 ms after stimulation with a long outward current pulse. Type B had a long time constant (18.8 +/- 5.7 ms) and a large a.h.p. (6.9 +/- 2.4 mV) with a medium half decay time of 203 +/- 90 ms. Type C was characterized by a long time constant (14.3 +/- 2.3 ms) and a large a.h.p. (6.5 +/- 1.5 mV) with a long half decay time of 478 +/- 230 ms. The slopes of the frequency-current (f-I) plots of the three types were different, particularly for the first spike interval. The slopes for the type A (414 +/- 102 impulses s-1 nA-1) and type B neurones (480 +/- 120 impulses s-1 nA-1) were steeper than that for the type C neurones (178 +/- 41 impulses s-1 nA-1). This difference is probably related to the relatively long first interval observed in the type C neurones. In all type B and a few type C neurones, when the membrane potential was hyperpolarized beyond--65 mV the application of orthodromic or direct stimulation generated a burst of spikes, consisting of a low-threshold response (l.t.r.) of low amplitude and superimposed high-frequency spikes. At the original resting potential, outward current pulses produced a train of low-frequency spikes. In type C neurones maintained in a depolarized state (about -50 mV), inward current pulses produced a specific delay of the return to the original membrane potential. This delayed return was thought to be generated by activation of a transient K+ (IA) conductance. Stimulation at the lateral edge of the v.m.h. produced excitatory post-synaptic potentials (e.p.s.p.s) in type A neurones, e.p.s.p.s with l.t.r. in type B neurones and e.p.s.p.-inhibitory post-synaptic potential sequences in type C neurones. About 20% of v.m.h. neurones, particularly the type C cells, were depolarized by glucose application with an associated increase in the input membrane resistance.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1986

Ionic basis for the electroresponsiveness of guinea-pig ventromedial hypothalamic neurones in vitro.

The difference between the ionic bases for electroresponsiveness in the three types of neurone in the ventromedial hypothalamic nucleus (v.m.h.) were studied in in vitro brain slice preparations of the guinea-pig. The current-voltage relationships in all three types of neurone showed anomalous rectification. Application of tetrodotoxin (TTX) abolished the fast action potentials in all three types of cell. In type A cells, injections of outward current pulses did not evoke spikes when the cells were perfused with TTX alone, but the addition of tetraethylammonium chloride elicited broad spikes. In type B and C cells, broad spikes could be evoked with TTX alone. These results suggest the presence of a minimal high-threshold Ca2+ current in type A neurones, and a more prominent one in type B and C neurones. In type B neurones, Ca2+ conductance blockage with Mn2+ or Co2+, or replacement of Ca2+ by Mg2+, abolished the low-threshold response (l.t.r.). Substitution with Ba2+ did not increase the duration of the l.t.r. significantly, suggesting that under normal conditions the falling phase of the response was caused by inactivation of Ca2+ conductance. In type B and C neurones, the amplitude and duration of the after-hyperpolarization (a.h.p.) following direct activation by long outward current pulses were markedly reduced in Ca2+-free solution. These findings indicate that a large component of this response was generated by the Ca2+-dependent K+ conductance increase. In type A cells the a.h.p. amplitude was originally small and was not affected by the above treatment, suggesting that the participation of this conductance was minimal in this type. In type C neurones, the membrane potential following an inward current pulse showed a delayed return to the base line. This delay was produced by transient K+ conductance, since it was reduced by 4-aminopyridine. The frequency-current (f-I) relation of the first interval in type A and C cells was scarcely affected in Ca2+-free solution, while the slope of the initial firing f-I curves in type B neurones which had the l.t.r. became flatter. Furthermore, the f-I curves of the third interval in type C cells became steeper in Ca2+-free solution. The data indicate that the distinct membrane characteristics related to the heterogeneity among cells in the v.m.h. can be attributed to their specific ionic mechanisms, with the type A neurones showing a minimal high-threshold Ca2+ current, the type B having l.t.r. and the type C having a transient K+ (IA) current.

Action Potentials↗