Regulation of the Catalytic Unit of Adenylate Cyclase System in Rat Brain

Ishibashi, Shun; Kurokáwa, Tomonori; Higashi, Kyoichiro; Dan'ura, Toshio

doi:10.1007/978-1-4684-4805-4_5

Cited by 4 publications

(1 citation statement)

References 19 publications

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“…The metal is a necessary component of glutamine synthetase (L-glutamate ammonia ligase; EC 6.3.1.2) which provides glutamine for synthesis of neurotransmitters (Wedler and Denman, 1984), and of mitochondria1 superoxide dismutase (EC 1.15.1.1) which serves to detoxify OXygen free radicals (Keen et al, 1984). The activities of numerous other enzymes and receptors within the brain change with altered [Mn] (Sadee et al, 1982;Ishibashi et al, 1984; Keen et al, 1984; Hegstrand and Kalinke, 1985; Qato and Maines, 1985). Mn deficiency increases seizure susceptibility in animals and may be related to seizure activity in humans (Keen et al, 1984;Prohaska, 1987).…”

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confidence: 99%

Saturable Transport of Manganese(II) Across the Rat Blood‐Brain Barrier

Murphy¹,

Wadhwani²,

Smith³

et al. 1991

Journal of Neurochemistry

139

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Unanesthetized adult male rats were infused intravenously with solutions containing 54Mn (II) and one of six concentrations of stable Mn(II). The infusion was timed to produce a near constant [Mn] in plasma for up to 20 min. Plasma was collected serially and on termination of the experiment, samples of CSF, eight brain regions, and choroid plexus (CP) were obtained. Influx of Mn (JMn) was calculated from uptake of 54Mn into tissues and CSF at two different times. Plasma [Mn] was varied 1,000-fold (0.076-78 nmol/ml). Over this plasma concentration range, JMn increased 123 times into CP, 18-120 times into brain, and 706 times into CSF. CP and brain JMn values fit saturation kinetics with Km (nmol/ml) equal to 15 for CP and 0.7-2.1 for brain, and Vmax (10(-2) nmol.g-1.s-1) of 27 for CP and 0.025-0.054 for brain. Brain JMn except at cerebral cortex had a nonsaturable component. CSF JMn varied linearly with plasma [Mn]. These findings suggest that Mn transport into brain and CP is saturable, but transport into CSF is nonsaturable.

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mentioning

confidence: 99%

Saturable Transport of Manganese(II) Across the Rat Blood‐Brain Barrier

Murphy¹,

Wadhwani²,

Smith³

et al. 1991

Journal of Neurochemistry

139

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3 Biological Significance of Manganese in Mammalian Systems

Wedler

1993

Progress in Medicinal Chemistry

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Actions of Lithium on the Cyclic AMP Signalling System in Various Regions of the Brain ‐ Possible Relations to its Psychotropic Actions ‐: A Study on the Adenylate Cyclase in Rat Cerebral Cortex, Corpus Striatum and Hippocampus

Mørk

1993

Pharmacology & Toxicology

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It has been estimated that in most industrialized countries 1 person out of every 1000 in the population is undergoing lithium treatment to stabilize their episodic mood disturbances due to manic-depressive illness. Lithium may stabilize mood swings by altering the action of certain neurotransmitters at the synaptic level in the brain. Recent research suggests that lithium alters neurotransmission by affecting neurotransmitter-coupled second messenger systems. A major second messenger system is the adenylate cyclase, which generates intracellular cAMP from ATP. The adenylate cyclases (type I-IV) are regulated by stimulatory and inhibitory receptors, which either stimulate or inhibit the adenylate cyclase activity. The stimulatory and inhibitory neurotransmitter-receptor signals are transferred to the catalytic unit of the adenylate cyclase by Gs and Gi, respectively. The activated receptor induces GTP stimulation of the heterotrimeric G protein, leading to a dissociation of the protein into the active alpha*GTP and the beta gamma complex. The former stimulates the catalytic unit of adenylate cyclase. The stimulation is terminated by a GTPase located on the alpha subunit that converts GTP to inactive GDP. At present, G proteins are known to play a central role in coupling receptors to effector proteins. In addition to extracellular regulation due to neurotransmitters, some adenylate cyclases (type I, III) are regulated by CaM as a consequence of enhanced intracellular concentrations of free Ca2+. The Ca(2+)-dependent stimulation of adenylate cyclase by CaM is assumed to occur by a direct effect on the catalytic unit. The catalytic units sensitive to Ca(2+)-CaM are also subjected to regulation by stimulatory and inhibitory neurotransmitter stimuli. Magnesium is essential for adenylate cyclase activity, since MgATP2- is the enzyme substrate. Furthermore, one Mg2+ site located on the G protein regulates both the receptor agonist affinity and the dissociation of the G protein during the activation cycle. A second Mg2+ site on the catalytic unit is responsible for Mg2+ regulation of the catalytic activity. The present work aimed at investigating the mechanisms by which lithium in vitro and after chronic treatment (ex vivo) affects adenylate cyclase activities in various regions of the rat brain. Lithium in vitro and ex vivo inhibited the selective stimulation of adenylate cyclase by Ca(2+)-CaM in the cerebral cortex. Furthermore, lithium in vitro interacted directly with the catalytic unit of adenylate cyclase.(ABSTRACT TRUNCATED AT 400 WORDS)

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Regulation of the Catalytic Unit of Adenylate Cyclase System in Rat Brain

Cited by 4 publications

References 19 publications

Saturable Transport of Manganese(II) Across the Rat Blood‐Brain Barrier

Saturable Transport of Manganese(II) Across the Rat Blood‐Brain Barrier

3 Biological Significance of Manganese in Mammalian Systems

Actions of Lithium on the Cyclic AMP Signalling System in Various Regions of the Brain ‐ Possible Relations to its Psychotropic Actions ‐: A Study on the Adenylate Cyclase in Rat Cerebral Cortex, Corpus Striatum and Hippocampus

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