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)

Prolyl-leucyl-glycinamide (MIF-1), the C-terminal tripeptide of oxytocin, and naloxone were administered intracranially (IC) to goldfish (Carassius auratus) in doses of 0.001, 0.01, 0.1, 1.0 and 10.0 mg/kg and compared to a diluent control group for their ability to reduce the effects of morphine (30 mg/kg IC) in an assay measuring analgesia to electric shock. Threshold levels of pain were determined by the voltage necessary to produce an agitated swimming response (ASR). Both MIF-1 and naloxone were found to significantly reduce the analgesic effects of morphine when compared to the diluent control group. Similar dose-response curves in an apparent sine-wave pattern were noted with both MIF-1 and naloxone when comparisons were made both at 20 minutes after administration of morphine and over the entire 150 minutes of the experiment. The results support the evidence that MIF-1 can act as an opiate antagonist.
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PMID:Similar antagonism of morphine analgesia by MIF-1 and naloxone in Carassius auratus. 612 44

Most neuropeptides are known to occur both in the central nervous system and in blood. This, as well as the occurrence of central nervous peptide effects after peripheral administration, show the importance of studying the relationships between the peptides in the two compartments. For many peptides, such as the enkephalins, TRH, somatostatin and MIF-1, poor penetration of the blood-brain barrier was shown. In other cases, including beta-endorphin and angiotensin, peptides are rapidly degraded during or just after their entry into brain or cerebrospinal fluid. Some peptides, such as insulin, delta-sleep-inducing peptide, and the lipotropin-derived peptides, enter the cerebrospinal fluid to a slight or moderate extent in the intact form. Many peptide hormones, such as insulin, calcitonin and angiotensin, act directly on receptors in the circumventricular organs, where the blood-brain barrier is absent. Oxytocin, vasopressin, MSH, and an MSH-analog alter the properties of the blood-brain barrier, which may result in altered nutritient supply to the brain. In conclusion, the diffusion of most peptides across the brain vascular endothelium seems to be severely restricted. There are, however, several alternative routes for peripheral peptides to act on the central nervous system. The blood-brain barrier is a major obstacle for the development of pharmaceutically useful peptides, as in the case of synthetic enkephalin-analogs.
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PMID:Minireview. Peptides and the blood-brain barrier. 630 42

Antidromically identified paraventricular neurones were recorded simultaneously with intramammary pressure in urethane (1.2 g/kg) anaesthetized rats during suckling. The correlation of the firing pattern of these neurones with milk ejection enabled distinction between oxytocin and vasopressin neurones. Oxytocin neurones displayed a short (2-6 s) characteristic high-frequency burst of spikes. This activation probably occurred simultaneously in all oxytocin neurones 12-18 s before milk ejection and was regular in both frequency and amplitude (total number of spikes). The role of neurohypophysial peptides and analogues in the control of these characteristics was studied. Injecting 10 pg, 100 pg and 1 ng of oxytocin into the 3rd ventricle increased background activity of slow-firing oxytocin neurones (less than 3 spikes/s) and had a strong dose-dependent facilitatory effect on the milk ejection reflex, increasing both the amplitude and frequency of neurosecretory bursts. No effect was observed on non-neurosecretory neurones. Such injection also triggered the milk ejection reflex when it had not appeared an hour after suckling began. Oxytocin did not itself induce neurosecretory activation, which only appeared if the young rats were sucking. Injecting oxytocin into the lateral ventricle was less effective than into the 3rd ventricle. No effect was observed after injection into the venous blood or into the 4th ventricle, which suggested that oxytocin acts in the hypothalamus. Injecting mesotocin or isotocin into the 3rd ventricle had a facilitatory effect similar to that of oxytocin but vasopressin, vasotocin, MIF I (pro-leu-gly-NH2, terminal triplet oxytocin) or bovine neurophysins I and II did not modify neurosecretory activation or the milk ejection pattern. Injecting an oxytocin antagonist, ([1(beta-mercapto-beta, beta cyclopentamethylene propionic acid), 8-ornithine] vasotocin, d(CH2)5OVT) into the 3rd ventricle decreased milk ejection frequency and considerably delayed the reappearance of the first milk ejection. This resulted from a decrease in both frequency and amplitude of neurosecretory bursts, which were too small to induce detectable oxytocin release. Moreover, d(CH2)5OVT suppressed the facilitatory effect of exogenous oxytocin. Under normal conditions, endogenous oxytocin seemed to be involved in the control of neurosecretory activation. Injecting 1 ng oxytocin or 1 or 10 ng vasopressin into the 3rd ventricle did not modify the firing pattern of vasopressin neurones whether activated by hyperosmotic stimulation (1 ml NaCl, 9% solution (w/v) I.P.) or not.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Electrophysiological evidence for facilitatory control of oxytocin neurones by oxytocin during suckling in the rat. 674 98

A large number of oxytocin (OT)-like neurons were detected in the sex segmental ganglia (SG5, SG6) of three species of leeches belonging to different orders: Theromyzon tessulatum, Hirudo medicinalis and Erpobdella octoculata. In this latter species, an epitope close to the vertebrate OT by its C-terminal part (MSH release inhibiting factor: MIF), localized in granules of a size diameter of ca 120 nm and colocalized with FMRFamide(FMRFa)-like material was demonstrated. With reverse phase-high performance liquid chromatography, evidence was given that the two epitopes (OT and FMRFa) colocalized in the same neurons were biochemically different. A titration of OT per SG indicated that the OT-like amount was considerably higher in sex SG than in non-sex SG (ca. 5 pmol vs. ca. 0.5 pmol). Moreover, at the level of sex SG, this amount was ca. 3-fold higher in immature leeches than in mature specimens. Injections of extracts of SG of E. octoculata and of fragments of OT (Tocinoic acid or MIF) to T. tessulatum, indicated that MIF (the epitope found in the sex SG) and sex SG have the same anti-diuretic effect on the leeches injected. These results pointed to an anti-diuretic role of the leech OT-like substance.
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PMID:Oxytocin-like peptide: a novel epitope colocalized with the FMRFamide-like peptide in the supernumerary neurons of the sex segmental ganglia of leeches--morphological and biochemical characterization; putative anti-diuretic function. 767 6

Annetocin, an oxytocin-related peptide recently isolated from the lumbricid earthworm Eisenia foetida, and putative transmitter substances were examined for their effects on rhythmic, spontaneous contractions of isolated gut preparations of the earthworm. Significant, dose-dependent effects of the following substances were observed: acetylcholine (ACh), gamma-aminobutyric acid (GABA), and dopamine were excitatory, while serotonin (5-HT) and octopamine were inhibitory. Annetocin, oxytocin, and vasotocin stimulated spontaneous contraction of the earthworm gut, annetocin being approximately 10-fold more potent than oxytocin or vasotocin. However, arginine-vasopressin (Arg-vasopressin), lysine-vasopressin (Lys-vasopressin), tocinoic acid (N-terminal hexapeptide fragment of oxytocin), and MSH release-inhibiting factor (MIF; C-terminal tripeptide fragment of oxytocin) did not show any effect on the earthworm gut motility. On the other hand, oxytocin, vasotocin, Arg-vasopressin, Lys-vasopressin, and tocinoic acid caused spontaneous contractions of isolated rat uterine preparations, where the potency was in this order, while annetocin and MIF exerted no oxytocic activity on the uterus. Dose-response relationship of the effects of annetocin and its related peptides on the annelid and mammalian systems shows that amino acid residue at the third position of these peptides is important for exertion of excitatory action on the smooth muscle systems. The results in the present study suggest that receptors for annetocin and for GABA on the earthworm gut, unlike those for ACh, desensitize during continuous exposure to these substances.
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PMID:Effects of annetocin, an oxytocin-related peptide isolated from the earthworm Eisenia foetida, and some putative neurotransmitters on gut motility of the earthworm. 779 Aug 42

Data available in the literature and the author's own findings of the effects of regulatory peptide (RP) and their analogues are summarized. MIF, TRH, and its analog PR-546, the paraopioid RP, leuenkephalin, dalargin, the ACTH analogue Semax, tafcin, thymosine, interleukin-1, vasopressin, oxytocin, bradykinin, defencin, and some proline-containing oligopeptides, such as Pro-Gly, Gly-Pro, Trp-Pro, Pro-Gly-Pro, Gly-Pro-Gly-Gly were studied. A complex of in vitro and in vivo tests identified three groups of RP: 1) neutral ones as to the hemostatic reactions studied; 2) stimulants of hypercoagulation and fibrin polymerization; 3) inhibitors of blood coagulation, increased fibrinolysis, and fibrin demopolymerization. The fibrinolytic and antithrombotic effects of Semax (in vivo), the procoagulative action of defencin, and the enhanced anticoagulant effects in the combinations of Semax-heparin and tafcin (in vivo) attract particular attention. Semax alone and in combination with heparin is recommended for clinical studies in respective hemostatic abnormalities.
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PMID:[The modulation of hemostatic reactions in vitro and in vivo by representatives of regulatory peptide families]. 892 38

MIF-1 (Pro-Leu-Gly-NH(2)) has potent therapeutic effects in depression and Parkinson's disease, but its CNS sites of production are not yet clear. In this study, the concentration of MIF-1 in different brain regions was measured by the multiple reaction monitoring technique on a 4000 QTRAP mass spectrometer. The limit of quantification was 300 fg of MIF-1, and limit of detection was 60 fg. The low molecular weight fractions of tissue homogenates from different regions of mouse brain were analyzed. The concentration of MIF-1 ranged from 22+/-3 fg/microg protein in cerebral cortex to 930+/-60 fg/microg protein in the hypothalamus. Moderate concentrations were also detected in all other regions tested, including the striatum, thalamus, and hippocampus. By incubation of stable isotope-labeled oxytocin with tissue preparations, it was also confirmed that oxytocin at least partially contributed to the production of MIF-1 in the hypothalamus by action of peptidases. Regional differences were also found. The results are the first to show the ultrasensitive quantification of MIF-1 in different brain regions, and support the neuromodulatory actions of MIF-1 in the striatum.
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PMID:Mass spectrometric quantification of MIF-1 in mouse brain by multiple reaction monitoring. 1954 Apr 26

In recent years, studies have advocated neuropeptide systems as modulators for the behavioral states found in mood disorders such as depression and anxiety disorders. Neuropeptides have been tested in traditional animal models and screening procedures that have been validated by known antidepressants and anxiolytics. However, it has become clear that although these tests are very useful, neuropeptides have distinct behavioral effects and dose-dependent characteristics, and therefore, use of these tests with neuropeptides must be done with an understanding of their unique characteristics. This review will focus on the behavioral actions of neuropeptides and their synthetic analogs, particularly in studies utilizing various preclinical tests of depression and anxiety. Specifically, the following neuropeptide systems will be reviewed: corticotropin-releasing factor (CRF), urocortin (Ucn), teneurin C-terminal associated peptide (TCAP), neuropeptide Y (NPY), arginine vasopressin (AVP), oxytocin, the Tyr-MIF-1 family, cholecystokinin (CCK), galanin, and substance P. These neuropeptide systems each have a unique role in the regulation of stress-like behavior, and therefore provide intriguing therapeutic targets for mood disorder treatment.
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PMID:Behavioral effects of neuropeptides in rodent models of depression and anxiety. 2002 11


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