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)

The effects of hydrogen ion concentrations on the carbon-13 nuclear magnetic resonance spectra of oxytocin were investigated. The starting pD of 3.0 was increased stepwise to 8.4. A change of the state of protonation of the N-terminal amino group of oxytocin is accompanied by changes in chemical shifts of carbon-13 nuclei of amino-acid residues located in the 20-membered ring of the hormone. The resonance positions of the acyclic peptide portion, Pro-Leu-Gly-NH(2), remain constant. The pD-induced chemical-shift changes of carbons up to five bonds removed from the site of protonation are interpreted in terms of "through-bond" and "through-space" mechanisms. Chemical-shift changes of carbons more than five bonds removed are proposed to have a conformational origin. It is suggested that a change in the charge density of the amino group perturbs the dihedral angle of the -CH(2)-S-S-CH(2)- moiety of oxytocin, which in turn significantly affects the overall conformation of the 20-membered ring of the hormone.
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PMID:Long-range, pH-dependent effects on the carbon-13 nuclear magnetic resonance spectra of oxytocin. 452 98

The 220 MHz spectra reported in this paper show the existence of cis-trans isomerism about the Cys-Pro bond in (S-benzyl)-L-Cys-L-Pro-L-Leu-Gly(NH(2)) and about the Z-Pro bond in (N-benzyloxycarbonyl)-L-Pro-L-Leu-Gly(NH(2)). These peptides are derivatives of the side chain of oxytocin, which has the structure L-Pro-L-Leu-Gly(NH(2)). Taken in water-free (CD(3))(2)SO, the spectra also show differences between the two isomers in the amide chemical shifts, which indicate interaction of the terminal end of the peptides with the rest of the residues. The ratio of the isomeric forms is about 2:3 for the S-benzylcysteinyl peptide, while it is 1:1 for the N-benzyloxycarbonyl-protected peptide. The probable assignment of peaks in isomers is discussed, in addition to routine spectral assignments based on extensive decoupling experiments.
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PMID:NMR studies on the conformation of derivatives of the side chain of oxytocin: examples of cis-trans isomerism. 527 99

The effects on oxytocin release of enkephalin analogues, thought to be highly selective agonists of the mu or delta opioid receptor, were compared. Oxytocin release was evoked in urethane-anaesthetised rats (7-10 days post partum) by intracerebroventricular injection of NaCl (3M) at 15-20 min. intervals and detected by the resultant increase in intramammary pressure. Enkephalin analogues (the mu receptor agonist Tyr-D-Ala-Gly-MePhe-NH (CH2)2OH (DAGO), the delta receptor agonist (D-Ala2-D-Leu5) - enkephalin (DADLE) and metkephamid, which has been reported to be particularly efficacious at the delta receptor) were administered intracerebroventricularly 3-5 min. prior to hypertonic saline. Oxytocin release was inhibited in a dose-dependent, naloxone-reversable manner by DAGO (ED50 : 40ng), DADLE (ED50 : 156ng) and metkephamid (ED50 : 42ng); the mammary gland sensitivity to oxytocin was unaffected. These results suggest that the inhibitory action may be mediated through both mu and delta receptors and provide further evidence in support of a role of enkephalins in the control of oxytocin secretion.
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PMID:Inhibition of oxytocin secretion by mu and delta receptor selective enkephalin analogues. 609 11

The hypothalamic peptide MIF-1 (Pro-Leu-Gly-NH2) was coupled to thyroglobulin and injected into rabbits. The resulting antiserum reacted with the tetrapeptide Tyr-MIF-1 to a greater extent than with the tripeptide MIF-1, presumably because of a better conformation for antibody binding. By radioimmunoassay (RIA), immunoreactive MIF-1/Tyr-MIF-1-like material was found in the pineal gland of each of the 100 rats examined. The tendencies for slightly higher levels in pineals obtained from rats kept in constant darkness for two weeks, from rats in a normal light cycle decapitated at noon, or from rats which had been hypophysectomized were not statistically significant. Gel filtration of pineal extracts on a column of Sephadex G-10 revealed that by RIA one immunoreactive peak eluted near MIF-1 and oxytocin, and another peak near Tyr-MIF-1. The results suggest the presence in pineal tissue of an MIF-1-like material as well as a novel peptide containing Tyr-Pro-Leu-Gly-NH2 or a closely related structure for which oxytocin is unlikely to be the precursor.
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PMID:Radioimmunoassay of MIF-1/Tyr-MIF-1-like material in rat pineal. 611 Oct 86

A test situation was developed in which the effects of drugs on habituation of exploratory behavior (head-poke responses) could be assessed independently of their effects on general activity (locomotion and rearing). Habituation, spontaneous recovery from habituation and stimulus specificity of habituation were studied. An amphetamine-barbiturate mixture attenuated habituation of the head-poke response without influencing general activity. Pro-Leu-Gly-NH2 (PLG), an oxytocin fragment, increased locomotor activity and did not alter the course of habituation of the head-poke response. Since exploratory behavior and general activity can be pharmacologically dissociated in the test situation used, it is concluded that the test situation is suitable for studying the effects of drugs on habituation of exploratory behavior. The amphetamine-barbiturate mixture did not influence the stimulus specificity of habituation of the head-poke response. Fenfluramine however increased the effects of stimulus change on the head-poke response while not influencing habituation of this response. These results show that habituation and stimulus specificity of habituation of exploratory behavior can be pharmacologically dissociated.
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PMID:Habituation of the head-poke response: effects of an amphetamine-barbiturate mixture, PLG and fenfluramine. 611 22

Pro-Leu-Gly-NH2 (PLG), which is the C-terminal tripeptide tail of oxytocin, has been reported to possess melanocyte-stimulating hormone (MSH)-release-inhibiting activity. Although it has been isolated from bovine hypothalamus, little is known about the CNS distribution of this peptide in other species. In this report, we describe the development of a radioimmunoassay which can be used to measure both PLG and oxytocin following chromatographic separation by high pressure liquid chromatography (HPLC). Using this method, we are unable to demonstrate the presence of any endogenous PLG in rat hypothalamus, preoptic area, pituitary, or eye tissue. However, synthetic PLG, which is added to tissue homogenates as an internal standard, is consistently recovered from all areas. We conclude that the PLG tripeptide is not present in the rat brain and thus cannot be the physiological regulator of MSH secretion.
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PMID:Development of a radioimmunoassay for Pro-Leu-Gly-NH2 (PLG or MIF-I): evidence that PLG is not present in rat brain. 612 41

1. A thiol proteinase from human pituitaries was purified approximately 400 fold and shown to have different chromatographic properties from that of calf brain. Among substrates cleaved were myelin basic protein, histones, beta-lipotropin, neurophysin, and Substance P. 2. The enzyme showed properties associated with a cathepsin-B like enzyme: dependence on -SH groups, pH optimum of 6.5, inhibition by leupeptin and a synthetic analog, Boc-D-Phe-Pro-arginal, and cleavage of dipeptidyl arylamides with basic residues adjacent to or penultimate to the chromatographic grouping. 3. Membranes present in the P2 fraction of rat brain contained three or more enkephalinases when submitted to DEAE-cellulose chromatography. Further purification on an IgG-Sepharose affinity column prepared with antibody to lung angiotensin converting enzyme indicated the presence of dipeptidyl carboxypeptidase(s) with properties distinct from those of ACE. In addition, the DEAE-cellulose fractions contained various aminopeptidase activities when tested with Leu-Gly-Gly, Leu-Nap, and Ala-Ala-Nap as substrates.
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PMID:Peptide processing in the central nervous system. 625 8

A post-proline cleaving enzyme and its endogenous inhibitor have been demonstrated to be present in sperm of the ascidian, Halocynthia roretzi. The enzyme was extracted with artificial sea water from frozen and thawed sperm and isolated from accompanying acrosin-like and chymotrypsin-like enzymes by DEAE-cellulose chromatography. It was then separated from the endogenous inhibitor by ammonium sulfate fractionation and DEAE-Sephacel chromatography. Three subsequent chromatographic operations using hydroxylapatite, Sephadex G-150 and Z-Gly-Pro-Leu-Gly-aminohexyl-Sepharose yielded the highly purified enzyme. The molecular weight and isoelectric point of the enzyme were estimated to be 66,000 and 5.5, respectively. The pH optimum of the activity was 7.0. The enzyme was inactivated with diisopropylphosphorofluoridate, phenylmethylsulfonyl fluoride, Z-Gly-Pro-chloromethyl ketone and sulfhydryl-directed reagents; these inhibitor susceptibilities were similar to those reported for the enzymes of mammalian origins. The ascidian enzyme hydrolyzed oxytocin, angiotensin II, luteinizing hormone releasing hormone and neurotensin at the carboxyl side of proline residues. The endogenous inhibitor was heat stable. The molecular weight of its main component was estimated to be about 8,000. The presence of salt at high concentrations weakened the enzyme-inhibitor interaction. Z-Gly-Pro-chloromethyl ketone inhibited fertilization of the ascidian, suggesting possible involvement of the post-proline cleaving enzyme in fertilization.
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PMID:Isolation and characterization of a post-proline cleaving enzyme and its inhibitor from sperm of the ascidian, Halocynthia roretzi. 636 Oct 7

A post-proline cleaving enzyme [prolyl endopeptidase, EC 3.4.21.26] was purified about 3,700-fold from an extract of bovine brain by a series of column chromatographies on DEAE-Sephadex, hydroxyapatite and PCMB-T-Sepharose, and gel filtration on Sephadex G-200 using N-carbobenzoxy-Gly-Pro-beta-naphthylamide (Z-Gly-Pro-2-NNap), thyrotropin releasing hormone (TRH) and oxytocin as substrates. The purified enzyme appeared homogeneous as judged by disc gel and SDS gel electrophoreses. The enzyme was most active at pH 7.5 and 7.2 with Z-Gly-Pro-2-NNap and TRH, respectively, and hydrolyzed peptide bonds involving Pro-X (X=amino acid, peptide, ester and amide) bonds of synthetic substrates, oxytocin, vasopressin, neurotensin, substance P, tuftsin, bradykinin, and insulin B chain. However, the enzyme was inert toward collagen, gelatin, and casein. The enzyme was completely inactivated by diisopropylphosphorofluoridate (DFP), Z-Gly-Pro-chloromethyl ketone and p-chloromercuribenzoate (PCMB), while it was not inhibited by phenylmethane sulfonylfluoride (PMSF) or metal chelators. Determination of the amino acid composition revealed that the enzyme contained 25 half-cystines. Modification of three cysteine residues of the enzyme by PCMB led to complete inactivation. The isoelectric point of the enzyme was 4.8, and the molecular weight was estimated to be 76,000 by ultracentrifugal analysis and 75,000-74,000 by both gel filtration and sodium dodecyl sulfate (SDS) gel electrophoresis, suggesting that the enzyme is present as a monomer. These results indicate that the post-proline cleaving enzyme from bovine brain is very similar to those previously purified from lamb brain and kidney in its enzymatic properties, substrate specificity and physicochemical properties, in sharp contrast with the results obtained by Tate, who reported that the bovine brain prolyl endopeptidase was inert toward oxytocin, vasopressin and bradykinin.
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PMID:Post-proline cleaving enzyme (prolyl endopeptidase) from bovine brain. 636 Oct 10

The influence of a i.v. injection of 2 I.U. of synthetic oxytocin (Oxy, Syntocinon) on plasma cortisol has been tested in 6 normal volunteers (age 22 to 33) and compared to a similar saline injection in a blind, cross-over design. Before injection basal cortisol is similar in Oxy (12.1 +/- 2.3 micrograms/100 ml M +/- Se) and saline (11.7 +/- 3.5) groups; in the Oxy group a significant (2 p less than 0.01) decrease of cortisol was noticed from the 45th min until the end of the test (120 min): the last mean level being 5.2 +/- 0.9 in the Oxy group compared to 12.9 +/- 1.8 in the saline group (2 p less than 0.005). Although the mechanism of action of Oxy on cortisol plasma levels remains to be investigated our results are in agreement with a proper action of Oxy and vasopressin at the level of the corticotroph cells or with a proper action of Oxy or of one of its metabolite (Pro-Leu-Gly-NH2 for example) on proopiomelanocorticotropic function.
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PMID:[Intravenous injection of synthetic oxytocin induces a decrease of cortisol plasma level in normal man]. 645 79


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