Neuropeptide inhibitors

Neuropeptide Inhibitors of Juvenile Hormone Synthesis in Brain and Corpora Allata of the Cockroach Diploptera punctata... 

C jjHjgNigOpS M 1411.644 Isol. from the brain of the cockroach Periplaneta americana. AUatostatin. Neuropeptide inhibitor. 

The effect of galanin and galanin fragments on histanrine release from ECL cells, showing that galanin is an effective neuropeptide inhibitor of ECL cell function and that the receptor is a galanin (Gal) 1 receptor subtype, based on a lack of response to Gal 9-29. 

In the trans Golgi compartment the peptide is sorted via secretory vesicles into a regulated pathway. In contrast to vesicles of the constitutive pathway, vesicles of the regulated pathway are stored in the cytoplasm until their stimulated release. Membrane depolarisation as well as a wide range of substances such as intracellular mediators, neuropeptides, neurotransmitters, classical hormones, cytokines, growth factors, ions and nutrients induce somatostatin secretion. General inhibitors of somatostatin release are opiates, GABA, leptin and TGF- 3. 

A neuropeptide Y (NYP) inhibitor is also being investigated as a possible weight loss drug. NYP inhibitors block a potent chemical, neuropeptide Y, which is an appetite stimulant. 

Holland et al. [125] have shown that the potent vascular smooth muscle cell mitogen and phospholipase A2 activator thrombin stimulated superoxide production in human endothelial cells, which was inhibited by the NADPH oxidase inhibitors. Similarly, thrombin enhanced the production of oxygen species and the expression of )Alphos and Rac2 subunits of NADPH oxidase in VSMCs [126,127]. Greene et al. [128] demonstrated that the activator of NO synthase neuropeptide bradykinin is also able to stimulate NADPH oxidase in VSMCs. Similar to XO, NADPH oxidase enhanced superoxide production in pulmonary artery smooth muscle cells upon exposure to hypoxia [129]. 

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. 

Neuronal loss Growth factors Synthetic neuropeptides Neuronal stem cells Growth factors Neuiite outgrowth activators Synaptogenesis activators Nogo inhibitors MOP inhibitors GSK-3 inhibitors JNK inhibitors AAV-NGF (CERE-110) Ceregene... 

Kavapyrones seem to be the therapeutically active constituents. Kava appears to influence a number of monoamine, amino acid, and neuropeptide transmitters in the CNS. Animal studies suggest that kava activates mesolimbic dopaminergic neurons (e.g., in the nucleus accumbens) while also altering 5-HT levels in various brain regions (Baum et ah, 1998). Kava may also act as a reversible MAO inhibitor and a noradrenergic reuptake inhibitor (Uebelhack et ah, 1998). 

Neuropeptide Y (NPY) is a potent inhibitor of neurotransmitter release through the Y2 receptor subtype.[99100] In the search for specific antagonists for the Y2 receptor, the concept of TASP has been applied by attaching four C02H-terminal peptide fragments of NPY (NPY 33-36) via oxime bonds to a cyclic template molecule containing two p-turn mimetics to result in T4-[NPY (33-36)]4, a potent selective antagonist of NPY at the Y2 receptor.1101-102 ... 

Neuropeptides are degraded by enzymes called neutral endopeptidases, which are present adjacent to neuropeptide receptors. Neutral endopeptidases regulate the neuropeptide-induced responses by modulating their levels. Inhibitors of these enzymes are being studied as a potential therapeutic agent for asthmatic disease. In... 

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