Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neurohypophysial preprohormones are single polypeptide chains folded into 3/4 domains, namely a signal prepeptide (18/20 residues), a hormone peptide (9 residues), and a propeptide neurophysin-copeptin (93/134 residues). Neuro-hormone and neurophysin contain 1 and 7 disulfide bridges, respectively, whose pairing depends on correct primordial folding within the endoplasmic reticulum (ER) compartment (pH 7.0) of hypothalamic magnocellular neurons. During intracellular travel in the secretory pathway from ER to secretory granules (SC), the precursor is submitted to successive processings (glycosylation, proteolysis, amidation) in distinct compartments, leading to domain separation and reshaping. In particular the hormone domain is subjected, in the SG, pH 5.5, to a 4-enzyme cascade in order to reach the bioactive conformation. We have purified SG from rat and ox neurohypophyses and characterized: 1) the processed domains (neurohormone, neurophysin, copeptin); 2) the four processing enzymes acting successively at the level of the processing sequence, namely a Lys-Arg calcium-dependent endopeptidase, a carboxypeptidase B-like enzyme, a peptidyl-glycine monooxygenase and a peptidyl-hydroxyglycine lyase (amidating enzyme). A reconstitution of the processing has been carried out in vitro using purified granular enzymes and synthetic nonactive prohormone peptides, vasopressinyl-Gly-Lys-Arg, vasotocinyl-Gly, and oxytocinyl-Gly. Vasopressin (yield 17% at pH 6.0, 30% at pH 8.0) has been identified by both coelution in high-performance liquid chromotography (HPLC) and bioactivity. In the homozygote mutant Brattleboro rats, a single nucleotide deletion in the gene entails a complete change in aminoacid sequence of neurophysin from residue 64 onwards. A misrouting in the ER or a misprocessing in the SG could occur so that neither vasopressin nor associated-neurophysin are found in the neurohypophysis, this lack determining diabetes insipidus. In addition there is a 50% decrease of the Lys-Arg-endoendopeptidase activity in the SG of the homozygote Brattleboro.
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PMID:Dynamic processing of neuropeptides: sequential conformation shaping of neurohypophysial preprohormones during intraneuronal secretory transport. 1205 40

Social cognition is impaired in patients with schizophrenia and is related to functional outcome. Neither current pharmacologic treatments for psychotic symptoms nor psychosocial interventions robustly improves measures of social cognition. Given this, the development of adjunctive treatments to improve functional outcome is a rational approach to treatment research in schizophrenia. The neuropeptide oxytocin is a candidate to treat deficits in social cognition due to its prosocial as well as anxiolytic effects. We report here results from a randomized, double-blind, parallel group 3 week clinical trial with daily administration of adjunctive intranasal oxytocin (20 IU twice daily) (n = 13) or placebo (n = 15). We examined the effect of oxytocin administration on measures of 4 domains of social cognition, as well as social functioning. After 3 weeks of oxytocin/placebo dosing, there was no significant difference favoring oxytocin between treatment groups in any outcome measure. These results add to the body of literature examining the effects of oxytocin on social cognition in schizophrenia. Further study is warranted.
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PMID:The Effect of Intranasal Oxytocin on Measures of Social Cognition in Schizophrenia: A Negative Report. 3103 74