Prolyl oligopeptidase (POP) is a ubiquitous post-proline cleaving enzyme that is highly expressed in brain. Current knowledge about the biochemical features of POP and the pharmacological action of its specific inhibitors has indicated that POP participates in several aspects of the central nervous system (CNS), including learning, memory and mood. Furthermore, a role has been suggested for POP in pathological processes such as eating and mood disorders, hypertension and cell-cycle disturbances, in addition to its proposed connection with the neurodegenerative processes which occur in Alzheimer's, Huntington's and Parkinson's diseases. The milestones responsible for the accelerated development of POP inhibitors include the discovery that these compounds reverse memory loss in animal models of drug- or lesion-induced amnesia and the observation that the expression of POP correlates with age. Today, several POP inhibitors have already been evaluated in preclinical trials as potential drugs for the treatment of natural memory deficits that occur with aging or the pathological memory loss characteristic of Alzheimer's disease. Thus, the results that are emerging from basic research on POP function will facilitate the fine-tuning of more efficient drugs to target this protease.
A series of disubstituted catechol derivatives was synthesized and tested as potential COMT inhibitors. The most active compounds were more than 1000 times more potent (IC50 = 3-6 nM) in vitro than the known COMT inhibitor, 3',4'-dihydroxy-2-methylpropiophenone (U 0521, IC50 = 6000 nM). The new compounds were also highly selective COMT inhibitors with no activity against other essential enzymes involved in the synthesis and metabolism of catecholamines.
Germinating wheat enzymes reduce the toxicity of wheat gliadin in vitro and ex vivo. Further studies are justified to develop an alternative therapy for celiac disease.
1 Neuropeptide Y (NPY) is one of the most potent stimulants of food intake. It has been debated which receptor subtype mediates this response. Initially Y 1 was proposed, but later Y 5 was announced as a`feeding' receptor in rats and mice. Very little is known regarding other mammals. The present study attempts to characterize the role of NPY in feeding behaviour in the distantly related guinea-pig. When infused intracerebroventricularly, NPY dose-dependently increased food intake. 2 PYY, (Leu 31 ,Pro 34 )NPY and NPY(2 ± 36) stimulated feeding, whereas NPY(13 ± 36) had no e ect. These data suggest that either Y 1 or Y 5 receptors or both may mediate NPY induced food intake in guinea-pigs. 3 The Y 1 receptor antagonists, BIBO 3304 and H 409/22 displayed nanomolar a nity for the Y 1 receptor (K i values 1.1+0.2 nM and 5.6+0.9 nM, respectively), but low a nity for the Y 2 or Y 5 receptors. When guinea-pigs were pretreated with BIBO 3304 and H 409/22, the response to NPY was inhibited. 4 The Y 5 antagonist, CGP 71683A had high a nity for the Y 5 receptor (K i 1.3+0.05 nM) without having any signi®cant activities at the Y 1 and Y 2 receptors. When CGP 71683A was infused into brain ventricles, the feeding response to NPY was attenuated. 5 The present study shows that NPY stimulates feeding in guinea-pigs through Y 1 and Y 5 receptors. As the guinea-pig is very distantly related to the rat and mouse, this suggests that both Y 1 and Y 5 receptors may mediate NPY-induced hyperphagia also in other orders of mammals.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.