Inhibition of in vitro amine uptake into rat brain synaptosomes after in vivo administration of antidepressants

The energy status (as measured by the ATP/ADP ratio), oxidative metabolism (14CO2 output) and neurotransmitter synthesis ([14C]acetylcholine production) by rat brain synaptosomes utilizing [U-14C]glucose has been studied. The ability of anoxia in vitro to permanently alter these parameters was investigated with reference to external [Ca2+] and [H+]. It has previously been shown that anoxic damage to synaptosomal preparations is only apparent when their metabolism is stimulated by veratridine [Harvey, Booth & Clark (1982) Biochem. J. 206, 433-439]. It is concluded that low [Ca2+] ameliorates, and high [H+] exacerbates, the damage sustained by veratridine-stimulated anoxic synaptosomes. The combined effects of low pH, anoxia and veratridine stimulation on synaptosomal metabolism most closely approximated to the irreversible damage to brain metabolism observed during acute hypoxia in vivo [Booth, Harvey & Clark (1983) J. Neurochem. 40, 106-110]. Suitably treated synaptosomal preparations may therefore be usefully employed as models to study impaired neurotransmitter synthesis in vivo.

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The correlation between Na+ channel subunits and scorpion toxin-binding sites. A study in rat brain synaptosomes and in brain neurons developing in vitro.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(19)57338-0 ◽

1988 ◽

Vol 263 (3) ◽

pp. 1542-1548

Author(s):

E Jover ◽

A Massacrier ◽

P Cau ◽

M F Martin ◽

F Couraud

Keyword(s):

Rat Brain ◽

Binding Sites ◽

Scorpion Toxin ◽

Na Channel ◽

Brain Neurons ◽

Rat Brain Synaptosomes ◽

Toxin Binding ◽

Brain Synaptosomes

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Vasopressin inhibits calcium-coupled sodium efflux system in rat brain

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1994.266.4.r1169 ◽

1994 ◽

Vol 266 (4) ◽

pp. R1169-R1173 ◽

Cited By ~ 4

Author(s):

F. Kanda ◽

A. I. Arieff

Keyword(s):

Rat Brain ◽

Neuronal Cell ◽

Atp Synthesis ◽

Sodium Efflux ◽

Rat Brain Synaptosomes ◽

Neuronal Membranes ◽

Brain Synaptosomes ◽

The Central Nervous System ◽

Na Uptake

Centrally released vasopressin plays an important role in the regulation of brain water and electrolyte composition and can affect brain intracellular pH and ATP synthesis in vivo. In this study, we evaluated the effects of [Arg8]vasopressin (AVP) on the Na(+)-Ca2+ exchanger, an important pathway in the regulation of cell Ca2+ concentration. It was found that AVP inhibited the Na(+)-Ca2+ exchanger in rat brain synaptosomes. This effect was completely blocked by the vasopressin V1-receptor antagonist d(CH2)5[(O-Me) Tyr2, Arg8]vasopressin. In addition, the vasopressin V2-receptor agonist 1-desamino-8-D-arginine vasopressin had no effect on the Na(+)-Ca2+ exchanger in rat brain synaptosomes. Depletion of intracellular Ca2+ by caffeine also had no effect on the effect of AVP on the Na(+)-Ca2+ exchanger. Na+ uptake by other pathways was also evaluated. It was found that AVP had no effect on Na+ uptake by pathways other than the Na(+)-Ca2+ exchanger. It is concluded that AVP inhibits the Na(+)-Ca2+ exchanger in neuronal membranes through vasopressin V1 receptors. Since this pathway is important in the regulation of cell volume and cytosolic Ca2+ in excitable tissue, AVP may impair neuronal cell repolarization in the central nervous system.

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