Neuropeptide signalling

Neurotransmission Neuropeptide signaling (Orexin receptor, Canna-binoid receptor, NAALAD2, Neurotensin receptors, Serotonin receptors, GABA A receptors. Metabotropic Glutamate receptors. Folate Hydro-lasel) Depression, Alzheimer s, Anxiety, Schizophrenia, Obesity, Urogenital... 

Set up an image acquisition file using the 4000 Series Explorer Software (Applied Biosystems) and check multiple regions of the tissue to ensure that sufificient neuropeptide signals can be detected (see Note 14). 

Neuropeptide S (NPS) is a recently discovered bioactive peptide that has emerged as a new signaling molecule in the complex circuitry that modulates sleep-wakefulness and anxiety-like behavior. The peptide precursor is expressed most prominently in a novel nucleus located in the perilocus coeruleus, a brain structure with well-defined functions in arousal, stress, and anxiety. NPS was also found to induce anxiolytic-like behavior in a battery of four different tests of innate responses to stress. Infusion of NPS potently increases wakefulness and suppresses non-REM (NREM) and REM sleep (Xu et al, 2004). NPS binds to a G-protein-coupled receptor, the NPS receptor, with nanomolar affinity activation of the receptor mobilizes intracellular calcium. The NPS receptor is expressed throughout the brain, particularly in regions relevant to the modulation of sleep and waking, in the tuberomammillary region, lateral hypothalamus, and medial thalamic nuclei. 

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]. 

Neuropeptides make a unique contribution to signaling 329 Regulation of neuropeptide expression is exerted at several levels 329... 

Probably the most striking difference between neuropeptides and conventional neurotransmitters is in their biosynthesis (Fig. 18-2). Neuropeptides are derived from larger, inactive precursors that are generally at least 90 amino acid residues in length [2-4]. The simplest example is prolactin, a pituitary product. The signal sequence for... 

The release of neuropeptides generally requires a more intense stimulus than that required for release of fastacting classical neurotransmitters. The more intense stimulus presumably results in more entry of Ca2+ into the presynaptic terminal, allowing Ca2+ to diffuse from its entry site to the LDCVs (Figs 18-3,18-4). As a result, the contribution of peptides vs. fast-acting conventional neurotransmitters to signaling can vary with the pattern of stimulation. For example, in Aplysia, several identified... 

Figure 5.3 displays a comparison of one-dimensional spectra of a neuropeptide in the presence of either DPC or SDS micelles at various pH values. Note that the signal at approx. 8.6 ppm due to HE1 of His vanishes in SDS at a much higher pH compared to DPC. In general, spectra in SDS still yield reasonable quality at neutral pH in contrast to those recorded in DPC. 

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