Neuropeptides and

Among vertebrate species, the neuro-endocrine-immime system is responsible for many complex, inter-related physiological processes including neuronal, homeostatic, reproductive and immune functions. There are four main types of hormone polypeptides, eicosanoids, steroids and thyroid hormones. Reflecting the inter-dependency of the neiiro-endocrine and immune systems, hormones, neuropeptides and other neiirotransmitters are known to be produced by some immune cells and play a role in the regulation of the immune system, while endocrine and nervous tissues express receptors for many substances produced by the immune system. The major focus of interest in endocrine disruption has... 

Diuretics This indicates the unique property of capsaicin-sensitive primary afferent neurons to release mediators (neuropeptides and others) from both peripheral and central nervous system terminals upon adequate stimulation. Capsaicin and other chemical (protons) or physical (heat) stimuli release mediators from both peripheral and... 

Extracellular degradation removes acetylcholine, the neuropeptides and ATP. Acetylcholine is rapidly hydrolyzed to choline and acetate by acetylcholinesterase. The enzyme is localized in both the presynaptic and the postsynaptic cell membrane and splits about 10,000 molecules of acetylcholine per second. 

Synaptic vesicles are the organelles in axon terminals that store neurotransmitters and release them by exocytosis. There are two types, the large dense-core vesicles, diameter about 90 nm, that contain neuropeptides, and the small synaptic vesicles, diameter about 50nm, that contain non-peptide transmitters. About ten vesicles per synapse are docked to the plasma membrane and ready for release, the readily releasable pool . Many more vesicles per synapse are stored farther away from the plasma membrane, the resting pool . When needed, the latter vesicles may be recruited into the readily releasable pool. Neuronal depolarization and activation of voltage-sensitive Ca2+... 

By far the most studied family of the G-protein-coupled receptors are the rhodopsin-like receptors. These are also the largest group of receptors in number as they include receptors not only for the monoamines, nucleotides, neuropeptides and peptide hormones, but they also include the odorant receptors which number several hundreds of related receptors. These receptors have short N-termini, a conserved disulphide bridge between the TM2-TM3 and TM4—TM5 extracellular domains, and variable-length C-termini. In some cases the C-terminus is myristolyated which by tying the C-terminus to the cell membrane generates a fourth intracellular loop. 

Darlison, MG and Richter, D (1999) Multiple genes for neuropeptides and their receptors coevolution and physiology. Trends Neurosci 22 81-88. 

Ritchie, JC and Nemeroff, CB (1991) Stress, the hypothalamic-pituitary-adrenal axis and depression. In Stress, Neuropeptides and Systemic Disease (Eds McCubbin, JA, Kaufmann, PG and Nemeroff, CB), Academic Press, London, pp. 181-197. 

Barnes, P.J. (1987). Airway neuropeptides and asthma. Trends Pharmacol. Sci. 8, 24-27. 

Figure 2 shows the elution profiles of several neuropeptides and the PCP-like material. When the PCP-active fractions were rechromatographed over a flatter gradient and in a different solvent system, it was clear that bombesin- and substance P-immunoreactiv-ity no longer coeluted with the PCP-like material. 

Sakurai, T., Amemiya, A, Ishii, M. el al. (1998). Orexins and orexin receptors a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell 92, 573-85. 

Hatzinger M (2000). Neuropeptides and the hypothalamic-pituitary-adrenocortical (HPA) system Review of recent research strategies in depression. World Journal of Biological Psychiatry, 1, 105-111. 

At the cellular level, eosinophils, mast cells, alveolar macrophages, lymphocytes and neutrophils recruited to the airways of asthmatics produce a variety of inflammatory mediators, such as histamine, kinins, neuropeptides, and leukotrienes, which lead to airway smooth muscle constriction and obstruction of airflow, and the perpetuation of airway inflammation [20, 21]. An understanding of the inflammatory processes and the molecular pathways of these mediators has led to the development and widespread use of several pharmacologic agents that mitigate airway inflammation and bronchoconstriction. 

Sulfation Influences biological activity of some neuropeptides and the proteolytic processing of some polypeptides... 

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... 

FIGURE18-4 Neuropeptides and conventional neurotransmitters are released from different parts of the nerve terminal. A neuromuscular junction containing both large dense-core vesicles (containing the neuropeptide SCP) and also small synaptic vesicles (containing acetylcholine) was stimulated for 30 min at 12 Hz (3.5 s every 7 s). Depletion of the small clear vesicles at the muscle face and of the peptide granules at the nonmuscle face of the nerve terminal was observed. After stimulation, there was an increase in the number of large dense-core vesicles within one vesicle diameter of the membrane. (Adapted from reference [37].)... 

Neuropeptides play key roles in appetite regulation and obesity. Many genes for neuropeptides and neuropeptide receptors have been implicated in obesity and cachexia, anorexia and bulimia [34]. For example,NPY administration into the CNS causes overeating and obesity. A second peptide involved in obesity is leptin, a product of adipocytes and the stomach. The leptin gene is defective in the ob/ob mouse but in normal mice leptin binds to its receptor in the hypothalamus, causing a decrease in the synthesis and release of hypothalamic NPY. 

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