Neuropeptides changes

Goadsby, P.J. and Edvinsson, L. The trigeminovascular system and migraine Studies characterizing cerebrovascular and neuropeptide change seen in human and cats, Ann. Neurol. 1993, 33, 48-56. 

Central nervous system Reduction of body weight Reduced appetite changed expression of anorexigenic (e.g., POMC) and orexigenic (e.g., NPY) hypothalamic neuropeptides... 

METH-induced changes in neuropeptide levels, selective Dj (SCH 23390) and D2 (sulpiride) dopaminergic receptor antagonists were coadministered. The results are expressed as percent of control to facilitate comparisons each value represents the mean SEM of five to seven animals. Data were subjeeted to either a Student s r-test (figures 4 and 5) or ANOVA analysis followed by a multiple comparisons test (figures 1, 2, and 3). Signifieanee was set at the. 05 level. 

Dyn is not yet known, it is likely that such changes reflect variations in the activity of the associated pathways. One possible explanation is that increases in neuropeptide tissue levels are due to decreased release of the transmitter, which dunmishes the extracellular peptide metabolism and results in accumulation of these peptide substances. Another possible contributing factor is a drug-related alteration in neuropeptide synthesis. For example, Bannon et al. (1987) reported that METH administration increased the quantity of striatal messenger RNA for the SP precursor preprotachykinin. Thus, increases in peptide synthesis might contribute to increases in peptide content caused by treatment with METH or the other amphetamine analogs. 

A8. Amalich, F., Sanchez, F. F., Martinez, M Jimenez, M., L6pez, J., Vazques, J. J., and Hernanz, A., Changes in plasma concentrations of vasoactive neuropeptides in patients with sepsis and septic shock. Life Sci. 56, 75-81 (1995). 

Several independent laboratories have now demonstrated that both lithium and valproate (VPA) exert complex, isozyme-specific effects on the PKC (protein kinase C) signaling cascade (reviewed in [3, 5, 11-13]). Not surprisingly, considerable research has recently attempted to identify changes in the activity of transcription factors known to be regulated (at least in part) by the PKC signaling pathway - in particular the activator protein 1 (AP-1) family of transcription factors. In the CNS, the genes that are regulated by AP-1 include those for various neuropeptides, neurotrophins, receptors, transcription factors, enzymes involved in neurotransmitter synthesis, and proteins that bind to cytoskeletal elements [14]. 

Mass spectrometry has been applied mainly in proteome research, but also in discovery and quantitation of neuropeptides that are involved in pain mechanisms, such as nocistatin, substance P, or verification of, for example, the structure of endogenous morphine in the central nervous system. Some proteomics studies of pain are aimed at the search for pain markers in cerebrospinal fluid, as it may reflect changes in brain and spinal cord functioning. Another research area concerns proteome analysis in cancer pain using spinal cord tissue and animal models. 

Several neurotransmitter and receptor changes are observed in Alzheimer s disease (Nordberg 1992). Losses occur in nicotinic receptors, but muscarinic receptors are relatively preserved. Reductions are also seen in serotonin 5-HTl and 5-HT2 receptors. Glutamate NMDA receptors decrease, while kainate receptors increase. j8-adrenergic and dopamine receptors are preserved. Decreases occur in receptors for somatostatin and neuropeptide Y, but corticotrophin-releasing factor receptors increase. Across all receptor subtypes for which there is a loss, the number of receptors decrease but the affinity constant remains unchanged. 

A calpain inhibitor, the DPK of N-dimethyltyrosine, was isolated from Streptomyces griseus and this compound showed activity in the calpain assay as described by Alvarez etal Calpain is a cytosolic protease regulated by calcium and is distributed in mammalian and avian cells. Calpain catalyzes proteolysis of target protein in cells, causing changes in metabolic processes such as the activation of protein kinase C, neuropeptide metabolism, and the activation of platelets. It is proposed that these inhibitors can be used in the treatment of neurodegen-erative diseases. 

Some authors (Flament et ah, 1987) found that response to treatment with clomipramine was correlated with a marked decrease in platelet serotonin concentration and monoamine oxidase (MAO) activity. Changes in cerebrospinal fluid (CSF) neuropeptides and monoamine metabolites have also been described with chronic clomipramine administration (Swedo et ah, 1992 Altemus et ah, 1994). Despite these observations, the exact mechanism of action of serotonergic drugs (and the serotonin hypothesis ) remains unproven, although it is thought they mediate their effects via down-regulation of the presynaptic 5-HTlD autoreceptor (Rauch et ah, 1994). 

Sheehan M, de Belleroche J Facilitation of GABA release by cholecystokinin and caerulein in rat cerebral cortex. Neuropeptides 3 429-434, 1983 Sherman AD, Petty F Additivity of neurochemical changes in learned helplessness and imipramine. Behav Neural Biol 35 344-353, 1982 Sherman WR Lithium and the phosphoinositide signaling system, in Lithium and the Cell. Edited by Birch NJ. London, Academic Press, 1991, pp 121-157 Sherman WR, Munsell LY, Gish BG, et al Effects of systemically administered lithium on phosphoinositide metabolism in rat brain, kidney, and testis. J Neurochem 44 798-807, 1985... 

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