Neuropeptides functions

Regulation of neuropeptide expression is exerted at several levels. Control of neuropeptide function is mediated by factors controlling rates of prepropeptide gene transcription, translation, peptide degradation and secretion (Fig. 18-11). On the scale of seconds to minutes, peptide secretion is not always coupled lock-step with classical transmitter release (example above). Peptides are inactivated by diffusion and by proteolysis, so it would be expected that inhibition of specific extracellular proteases... 

Since the enzyme machinery to manufacture more monoamines is present in axon terminals (Fig. 1—7), additional monoamine neurotransmitters can be synthesized there. Since a reuptake pump, which can recapture released monoamines, is present on the presynaptic neuron (Fig. 1—8), monoamines used in one neurotransmission can be captured for reuse in a subsequent neurotransmission. This is in contrast to the way in which neuropeptides function in neurotransmission (Fig. 1—9). 

Albers HE, Liou S-Y, Stopa EG, Zoeller RT (1991) Interaction of colocalized neuropeptides functional significance in the circadian timing system. J Neurosci 77 846-851. 

Widerlov, E., Wahlestedt, C., Hakanson, R. Ekman, R. (1986) Altered brain neuropeptide function in psychiatric illness - with special emphasis on NPY and CRF in major depression. Clin. Neuropharmacol. 9, 572-574. 

Penzlin, H. Baumann, E. In Comparative Aspects of Neuropeptide Function, Florey, E. Stefano, G. B., Eds. Manchester University Manchester, United Kingdom, 1991 pp 222-32. 

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... 

The first idea to consider is the effect of receptor density on sensitivity of a functional system to agonists. Clearly, if quanta of stimulus are delivered to the stimulus-response mechanism of a cell per activated receptor the amount of the total stimulus will be directly proportional to the number of receptors activated. Figure 5.8 shows Gi-protein-mediated responses of melanophores transiently transfected with cDNA for human neuropeptide Y-l receptors. As can be seen from this figure, increasing receptor expression (transfection with increasing concentrations of receptor cDNA) causes an increased potency and maximal response to the neuropeptide Y agonist PYY. 

FIGURE 5.10 Effects of co-expressed G-protein (G ) on neuropeptide NPY4 receptor responses (NPY-4). (a) Dose-response curves for NPY-4. Ordinates Xenopus laevis melanophore responses (increases light transmission). Ordinates logarithms of molar concentrations of neuropeptide Y peptide agonist PYY. Curves obtained after no co-transfection (labeled 0 jig) and co-transfection with cDNA for Gai6. Numbers next to the curves indicate jig of cDNA of Ga]g used for co-transfection, (b) Maximal response to neuropeptide Y (filled circles) and constitutive activity (open circles) as a function of pg cDNA of co-transfected G g. 

Neuromedin U is a neuropeptide which is widely distributed in the gut and central nervous system. Peripheral activities of neuromedin U include stimulation of smooth muscle, increase in blood pressure, alteration of ion transport in the gut, control of local blood flow and regulation of adrenocortical function. The actions of neuromedin U are mediated by G-protein coupled receptors (NMU1, NMU2) which are coupled tO Gq/11. 

Cerda-Reverter JM, Larhammar D (2000) Neuropeptide Y family of peptides structure, anatomical expression, function, and molecular evolution. Biochem Cell Biol 78 371-392... 

The neuropeptide Y (NPY) belongs to a family of peptides that includes peptide YY and pancreatic polypeptide, and it is associated with several diseases such as asthma, immune system disorders, inflammatory diseases, anxiety, depression and diabetes mellitus. NPY is found in the central and peripheral nervous system, and its biological functions are mediated by interactions with five receptor sub-types, i.e. Yl, Y2, Y4, Y5 and Y6. Several studies indicate that the feeding behavior is influenced by interactions between NPY and Yl and Y5. Deswal and Roy used Cerius descriptors and genetic function approximation QSAR to investigate the structural determinants for the inhibition potency of 24 compounds with the general structure 4 for the NPY Y5 receptor [31]. The best QSAR (H = 0.720,... 

---