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  • 1
    Electronic Resource
    Electronic Resource
    Energy on demand: a mechanism for astrocyte–neuron metabolic coupling (2003)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 85 (2003), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: A tight link exists between neuronal activity and energy metabolism. This relationship was first proposed by Roy and Sherrington who suggested that brain possesses intrinsic mechanisms to regulate the availability of energy substrates in register with local variations of functional activity. This concept was later confirmed by Sokoloff and colleagues who demonstrated that increased neuronal activity led to increased glucose utilization in almost any areas of the brain tested. Despite wide acceptance of this concept, the cellular and molecular mechanisms that underlie this close relationship between neuronal activity and energy metabolism have remained largely unknown. The extensive analysis carried out by our group will be discussed. Astrocytes appear to be the key cells that operate the coupling between synaptic activity and glucose utilization. Indeed both in vitro and in vivo evidences indicate that astrocytes can detect synaptically released glutamate through sodium-coupled uptake operated by glutamate transporters. Disruption of sodium homeostasis activates the energy-demanding Na-K-ATPase which promotes glucose uptake and lactate production. Relevance of these findings to functional brain imaging will be discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.85.s2.2_1.x
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  • 2
    Electronic Resource
    Electronic Resource
    Modulation of VIP-Stimulated cAMP Formation by Excitatory Amino Acids in Mouse Cerebral Cortex (1990)
    Oxford, UK : Blackwell Publishing Ltd
    European journal of neuroscience 2 (1990), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: We have investigated the modulatory action of excitatory amino acids (EAA) on vasoactive intestinal polypeptide (VIP)-stimulated cAMP formation in mouse cerebral cortical slices. Glutamate and aspartate potentiate in a concentration-dependent manner the effect of VIP. In order to characterize the type of receptor involved, we have used three prototypical EAA receptor agonists, that is, kainate, N-methyl-D-aspartate (NMDA) and quisqualate. Kainate mimicked the effect of glutamate, NMDA was inactive and quisqualate displayed an inhibitory action. Furthermore, ibotenate also potentiated the effect of VIP on cAMP formation, while L-homocysteate exhibited an inhibitory action. Ibotenate was 4-fold more potent and 2.5 times more effective than glutamate. However, the effects of kainate and ibotenate were not additive, suggesting the activation of a common receptor. Thus, based on this metabotropic action, EAA can be categorized into the following classes: (i) those that potentiate the effect of VIP, such as glutamate, aspartate, kainate and ibotenate; (ii) those that inhibit the effect of VIP, such as L-homocysteate and quisqualate; and (iii) those that are ineffective, such as NMDA and D-homocysteate. The effects of glutamate or ibotenate on VIP-stimulated cAMP formation were completely inhibited by L-phosphoserine and only partially by kynurenate. In a low chloride medium, or in the presence of 8-(N,N-diethylamino) octyl-3,4,5-trimethoxybenzoate-hydrochloride (TMB-8), an inhibitor of calcium release from internal stores, EAA did not potentiate the effect of VIP, thus stressing the importance of these ions for the transduction of the glutamatergic signal. Our results indicate the existence of marked interactions between EAA and VIP on cAMP formation; the pharmacology of these interactions is, however, clearly distinct from the classical pharmacology of EAA which is mainly based on electrophysiological and binding studies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1460-9568.1990.tb00443.x
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  • 3
    Electronic Resource
    Electronic Resource
    Dopaminergic supersensitivity induced by denervation and chronic receptor blockade is additive (1982)
    [s.l.] : Nature Publishing Group
    Nature 299 (1982), S. 72-74 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Male Sprague-Dawley rats (Charles River Laboratories; mean weight 305 g) were used. To study denervation super-sensitivity, 8 jjig of 6-hydroxydopamine were injected into the nucleus accumbens on each side as previously described14. Sham-treated control subjects were prepared with bilateral ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/299072a0
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  • 4
    Electronic Resource
    Electronic Resource
    Cellular Mechanisms of Brain Energy Metabolism. Relevance to Functional Brain Imaging and to Neurodegenerative Disorders (1996)
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 777 (1996), S. 0 
    Details
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Notes: Astrocyte end-feet surround intraparenchymal microvessels and represent therefore the first cellular barrier for glucose entering the brain. As such, they are a likely site of prevalent glucose uptake. Astrocytic processes are also wrapped around synaptic contacts, implying that they are ideally positioned to sense and be functionally coupled to increased synaptic activity. We have recently demonstrated that glutamate, the main excitatory neurotransmitter, stimulates in a concentration-dependent manner 2-DG uptake and phosphorylation by astrocytes in primary culture.1 The effect is not receptor-mediated but rather proceeds via one of the recently cloned glutamate transporter. The mechanism involves an activation of the Na+/K+ ATPase. Concomitant to the stimulation of glucose uptake, glutamate causes a concentration-dependent increase in lactate efflux. These observations suggest that glutamate uptake is coupled to aerobic glycolysis in astrocytes. In addition, since glutamate release occurs following the modality-specific activation of a brain region, the glutamate-evoked uptake of glucose into astrocytes provides a simple mechanism to couple neuronal activity to energy metabolism. These data also suggest that modality-specific activation visualized using 2DG-based autoradiography or PET may primarily reflect glutamate-mediated uptake of 2DG into astrocytes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1749-6632.1996.tb34449.x
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  • 5
    Electronic Resource
    Electronic Resource
    Effects of dobutamine on cyclic AMP accumulation induced by the stimulation of dopamine receptors in rabbit retina in vitro (1980)
    Springer
    Cellular and molecular life sciences 36 (1980), S. 1108-1110 
    Details
    ISSN: 1420-9071
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Intact rabbit retinae were used for testing in vitro the potential activation of dopamine receptors by a new cardioactive sympathetic amine dobutamine. It was found that despite the structure relationship of dobutamine with other dopamine-analogs, the pharmacological action of this compound is not comparable to that of apomorphine, N-methyl-dopamine and/or ADTN.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01965998
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  • 6
    Electronic Resource
    Electronic Resource
    Differential effects of benzamides and thioxanthenes on dopamine-elicited accumulation of cyclic AMP in isolated rabbit retina (1978)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 303 (1978), S. 189-191 
    Details
    ISSN: 1432-1912
    Keywords: Dopamine ; Sulpiride ; Thioxanthenes ; Retina ; Cyclic AMP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Benzamides or thioxanthenes were tested as potential antagonists of the cyclic AMP accumulation induced by 10−4 M dopamine in intact rabbit retinae in vitro in the presence of 5 to 7 mM theophylline. The neuroleptic sulpiride (10−4 M) was found to be totally inactive whereas a substituted benzamide (clebopride) had small but significant antagonist effect at the same concentration. Among thioxanthenes, isomers of cisconfiguration, which are potent neuroleptics, completely inhibit the cyclic AMP accumulation induced by dopamine, in contrast to trans-isomers which had no inhibitory effects. These data would confirm that retina in vitro is another suitable model for screening antipsychotic activity of classical neuroleptics and that the mechanism of action of sulpiride still needs further investigation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00508067
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  • 7
    Electronic Resource
    Electronic Resource
    Fresh human islet transplantation to replace pancreatic endocrine function in type 1 diabetic patients (1991)
    Springer
    Acta diabetologica 28 (1991), S. 151-157 
    Details
    ISSN: 1432-5233
    Keywords: Islet allograft ; Type 1 ; insulin-dependent diabetes mellitus ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of this study was to evaluate the feasibility of islet allografts in patients with type 1 diabetes melititus. Six patients received human islets from either one or two donors via the portal vein, after (n=4) or simultaneously with (n=2) a kidney graft. The patients with functioning kidney grafts (nos. 1–4) were already on triple immunosuppressive therapy (cyclosporine A, azathioprine, prednisone). Prednisone was increased to 60 mg/day for 15 days after the islet transplant in patient 1. Patient 2–4 and the patients who underwent a simultaneous kidney-islets graft (nos. 5, 6) also received antilymphocyte globulin. Intravenous insulin was given for the first 15 days to maintain blood glucose concentrations within the normal range. Patient 1 rejected the islets within 15 days of islet transplantation. In patient 2, a 25% reduction in insulin requirement was observed and 12 months after transplantation post-prandial serum C-peptide was 1.5 ng/ml. In patient 3, the insulin requirement decreased from 40 to 8 units/day with a post-prandial serum C-peptide of 4.1 ng/ml 12 months after islet transplantation. In patient 4 the post-prandial secretion of C-peptide increased to 6.4 ng/ml. Six months after the islet infusion, insulin therapy was discontinued and HbA1c, 24-h metabolic profile and oral glucose tolerance test remained within the normal range. He had remained off insulin for 5 months until recently, when foot gangrene paralleled a worsening of post-prandial glycaemic control. Twelve months after transplantation he is receiving 8 units insulin/day. Patients 5 and 6 received a simultaneous kidney and islet graft and 6 months after transplantation their post-prandial C-peptide secretion peaks were 2.5 and 1.9 ng/ml respectively. Their daily insulin requirement was not significantly modified. In conclusion, these results show that an adequate number of human islets injected intraportally in type 1 diabetic patients can replace the pancreatic endocrine function and can lead to insulin independence.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00579718
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  • 8
    Electronic Resource
    Electronic Resource
    Delineation of epileptic focus by single photon emission tomography (1982)
    Springer
    European journal of nuclear medicine 7 (1982), S. 484-485 
    Details
    ISSN: 1619-7089
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00253088
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