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)

Cytosolic aminopeptidase P was obtained in highly purified form from human leukocytes by a four-step procedure. Buffy coats were the starting material. A M(r) of 140,000 was obtained by size-exclusion HPLC for the native enzyme. As shown by SDS/PAGE under reducing and denaturing conditions, the enzyme consisted of likely identical subunits with M(r) of 71,000. Purified aminopeptidase P cleaved off, specifically and efficiently, the N-terminal residues from peptides with N-terminal Xaa-Pro sequences. The penultimate proline was not replaceable by hydroxyproline, alanine and glycine in di-, tri- and tetrapeptides. Polyproline was not hydrolyzed. Dipeptides were cleaved (Arg-Pro, Phe-Pro > Trp-Pro > Pro-Pro) although slower than longer peptides. Cleavage was observed of several biologically active peptides; C-terminal fragment (residues 201-206) of C-reactive protein, oxytocin fragment Tyr-Pro-Leu-Gly, morphiceptin, peptide Gly-Pro-Arg-Pro (inhibitor of fibrin polymerization) and kentsin. In addition, cleavage of a protein, interleukin-6, was also demonstrated. Aminopeptidase P was maximally activated by Mn2+, and to a lesser extent by Co2+. The activity was optimal at pH 8. Ni2+, Zn2+ and especially Cd2+ caused marked inhibition. EDTA, 1,10-phenantroline and dithiothreitol were also inhibitory. Carbobenzoxy-phenylalanine, as well as several N-carbobenzoxy-proline-containing peptides, caused partial inhibition. The observed resistance of Gly-Pro, Pro-Gly, Pro-Phe and Pro-Ile to hydrolysis by the purified enzyme strongly indicates absence of known proline-specific dipeptidases in the aminopeptidase-P preparation.
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PMID:Aminopeptidase P from human leukocytes. 144 89

Recently, we have described a chorionic peptidase (C-ase-1) which inactivates gonadotropin releasing hormone (GnRH), oxytocin, angiotensin II and thyrotropin releasing hormone. Since all these hormones contain a proline residue, we proposed that C-ase-1 may act as a post-proline peptidase. Using HPLC and amino acid analyses, we have defined the products which resulted from enzymatic inactivation of GnRH by C-ase-1. The N-terminal nonapeptide of GnRH was isolated by HPLC and confirmed by amino acid composition analyses. Thus, it was demonstrated that C-ase-1 acts as a post-proline peptidase when inactivating GnRH, yielding the nonapeptide, i.e., des-Gly10-NH2-GnRH, and Gly-NH2. The levels of intrauterine GnRH, angiotensin II, oxytocin and thyrotropin releasing hormone may be affected and integrated by this enzyme. Thus, C-ase-1 may play an important role in the regulation of the paracrine and endocrine function during pregnancy.
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PMID:Chorionic peptidase inactivates GnRH as a post-proline peptidase. 150 38

Human granulosa cells synthesize and secrete the oxytocin hormone. We have already shown that oxytocin-Gly, the last post-translational maturation intermediate of pro-hormone, is largely secreted by cultured granulosa cells deprived of ascorbate (Plevrakis et al. (1990) J. Endocrinol. 124, R5-R8). Using a combination of high performance liquid chromatography and radioimmunoassay, the oxytocin-like material present in human granulosa cell extracts, in follicular fluid, in cultured granulosa cell supernatants and in corpora lutea extracts was identified. We have demonstrated the presence of oxytocin-Gly, oxytocin-Gly-Lys and oxytocin-Gly-Lys-Arg, the same post-translational maturation intermediates as those we identified in bovine corpus luteum secretory granules. Thus we conclude that post-translational maturation of pro-oxytocin/neurophysin in human ovary proceeds by the same proteolytic events as those we described in bovine post-pituitary gland and corpus luteum.
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PMID:COOH-terminally-extended processing forms of oxytocin in human ovary. 154 13

An oxytocin/vasopressin-immunoreactive peptide was isolated from nerve terminals of the 'neurosecretory system of the vena cava' in octopus. It was purified by HPLC combined with a RIA for oxytocin. Characterization of the peptide by automated Edman degradation, plasma desorption mass spectroscopy, enzymatic treatment and coelution experiments resulted in the structure: Cys-Tyr-Phe-Arg-Asn-Cys-Pro-Ile-Gly-NH2, a nonapeptide with a molecular weight of 1070 Da and a 1-6 disulfide bond. This cephalopod neuropeptide, here called 'cephalotocin', exhibits 78% sequence homology with the vertebrate neurohypophysial hormone mesotocin and clearly belongs to the oxytocin/vasopressin family of vertebrates, confirming the high conservation of this peptide family.
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PMID:A new peptide of the oxytocin/vasopressin family isolated from nerves of the cephalopod Octopus vulgaris. 158 45

Vasopressinyl-Gly-Lys-Arg, the first intermediate derived from vasopressin protein precursor, has been converted into mature vasopressin by an "in vitro" two-step reaction through neurohypophysial secretory granule enzymes. Whereas the conversion into vasopressinyl-Gly is virtually complete at pH 5.5 as judged by HPLC, the conversion of vasopressinyl-Gly into vasopressin is weak at pHs 6.0 or 8.0 as judged by HPLC and measure of generated pressor activity. It is suggested that the high conversion yield usually seen in mammalian neurohypophysis, where no intermediate is detected, might be due to additional "in vivo" factors such as particular membrane-association or binding of the intermediate onto a neurophysin carrier.
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PMID:Partial conversion of vasopressinyl-Gly-Lys-Arg into pharmacologically active vasopressin through secretory granule carboxypeptidase E and alpha-amidating processing enzymes. 161 Mar 78

We synthesized 10 analogs (1-10) derived from the sequence of [Pmp1,D-Trp2,Arg8]oxytocin, (parent antagonist or PA), (Pmp = beta,beta-pentamethylene-beta-mercaptopropionic acid) which is a potent antagonist (pA2 = 7.77) of the uterotonic effect of oxytocin (OT) in rats, as determined in our uterotonic assay. Eight of the following analogs were designed by replacement of each residue in the PA sequence, other than the residue at position 2, with D-tryptophan: Ac-D-Trp-D-Trp-Ile-Gln-Asn-Val-Pro- Arg-Gly-NH2, (1); [Pmp1,D-Trp(For)2,Arg8] OT, (2); [Pmp1,D-Trp2,D-Trp3,Arg8] OT, (3); [Pmp1,D-Trp2,D-Trp4,Arg8] OT, (4); [Pmp1,D-Trp2,D-Trp5,Arg8] OT, (5); Aaa-D-Trp-Ile-Gln-Asn-D-Trp-Pro-Arg- Gly-NH2, (6); [Pmp1,D-Trp2,D-Trp7,Arg8] OT, (7); [Pmp1,D-Trp2,D-Trp8] OT, (8); [Pmp1,D-Trp2,Arg8,D-Trp9] OT, (9); [Pmp1,D-Trp2,Arg8,D-Trp(For)9] OT, (10). To avoid free mercaptan groups, Val6 was chosen in analog 1 instead of Cys and Aaa1 (Aaa = 1-adamantaneacetic acid) in analog 6 instead of Pmp1. Of the linear analogs, 1 was inactive as an OT antagonist and 6 was a very poor antagonist, with a pA2 = 5.66, but it was more potent than Aaa-D-Trp-Ile-Gln-Asn-Val-Pro-Arg-Gly-NH2, which has a pA2 = 5.33, as we had previously reported. Analog 2, featuring D-Trp(For)2, pA2 = 7.37, was weaker than PA, indicating that the formyl group lowers potency. Analogs 3 and 4 were much weaker than PA, and analog 5 was inactive. Hence, other than at position 2, D-Trp is undesirable in the ring sequence of PA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Some pharmacological properties of cyclic and linear analogs obtained by substituting each residue of an oxytocin antagonist with D-tryptophan. 178 91

Human MSEL-neurophysin has been dissected into two halves by endopeptidase Lys-C, taking advantage of a peculiar Lys59-Ala60 bond. Two sub-domains, N-terminal (1-59) and C-terminal (60-93), have been separated. These sub-domains have been purified by reverse-phase high pressure liquid chromatography and identified by their N-terminal sequences. The N-terminal fragment comprises two chains 1-18 and 19-59, because of the presence of a second lysine residue in position 18, whereas the C-terminal fragment (60-93) is a single chain. Hormone-binding experiments have been carried out using vasopressin or vasopressinyl-Gly-Lys-Arg and testing the ability of the hormone-neurophysin complex to precipitate at pH 3.9 with 10% NaCl. The N-terminal sub-domain precipitates in presence of vasopressin in the same way as native neurophysin whereas the C-terminal sub-domain does not. It can be concluded that the hormone-binding site is located in the 1-59 region of neurophysin.
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PMID:The hormone-binding site of neurophysins: binding of vasopressin to the N-terminal sub-domain dissected from human MSEL-neurophysin through endopeptidase Lys-C. 181 3

Bovine corpus luteum is the site of intense production of pro-ocytocin-neurophysin mRNA at day 1 after estrus (Ivell et al. (1985) FEBS Lett. 190, 263-267) which is followed by apparent delayed production of ocytocin. Therefore it is a good model to study both the translational and post-translational production of this neuropeptide in non-hypothalamic tissues and its regulation. In order to assess if this mRNA is translated during the lag period we have analyzed the neurophysin-like species produced in this organ. As early as day 2 after estrus one neurophysin species (pI approximately 4.7) could be detected and was unequivocally identified as pro-ocytocin-neurophysin. In primary cultures of luteinizing granulosa cells, biosynthetic intermediates were characterized, i.e. ocytocin-Gly, ocytocin-Gly-Lys and ocytocin-Gly-Lys-Arg, whereas amidated, fully mature, ocytocin was undetectable. We conclude that translation of pro-ocytocin-neurophysin mRNA takes place soon after transcription and we propose that incomplete processing could be responsible for the low level of ocytocin in the early bovine corpus luteum.
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PMID:Synthesis and processing of pro-ocytocin in bovine corpus luteum and granulosa cells. 181 98

We prepared nine analogues (1-9) of MCPA-D-Phe-Phe-Ile-Asn-Cys-Pro-Arg-Gly-NH2, [MCPA1, D-Phe2, Phe3, Ile4, Arg8]oxytocin (MCPA = beta-mercapto-beta,beta-pentamethylenepropionic acid), a potent antagonist of the rat uterotonic action of oxytocin (OT). We replaced D-Phe with D-Trp and made [MCPA1,D-Trp2,Phe3,Ile4,Arg8]OT (1), which had OT pA2 of 7.51, somewhat higher than that of the D-Phe2 antagonist which has OT pA2 = 7.35 in our rat uterotonic assay. Both compounds are equipotent as antagonists of [Arg8]vasopressin in the rat antidiuretic assay, with pA2 = 8.1. Other substitutions gave [MCPA1,D-Trp2,4-Cl-Phe3,Ile4,Arg8]OT, (2), OT pA2 7.44; [MCPA1,D-Trp2,Phe3,Ile4,3,4-dehydro-Pro7,Arg8]OT (3), OT pA2 = 7.42; [MCPA1,D-Trp2,Phe3,Arg8]OT (4), OT pA2 = 7.58; [MCPA1,D-Trp2,Phe3,Arg8,Gly9-NHEt]OT (5), OT pA2 = 7.49; [MCPA1,D-Trp2,Ile4,Arg8]OT (6), OT pA2 = 7.46; [MCPA1,D-Trp2,Val4,Arg8]OT (7), OT pA2 = 7.58; [MCPA1,D-Trp2,Thr4,Arg8]OT (8), OT pA2 = 7.48; and finally, [MCPA1,D-Trp2,Arg8]OT (9), which was a more potent and more selective OT antagonist, with OT pA2 = 7.77 in the uterotonic assay and ADH pA2 less than 5.9 in the antidiuretic assay and hence is an important lead for the design of OT antagonists.
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PMID:Design of potent oxytocin antagonists featuring D-tryptophan at position 2. 199 88

Although neurohypophysial peptides are present in many regions of the developing and adult bullfrog (Rana catesbeiana) brain, the function of these peptides remains unclear. To investigate possible behavioral actions, we examined locomotor activity following peptide injection in bullfrogs at various developmental stages. An intraperitoneal (ip) injection of arginine vasotocin (AVT) in tadpoles (stages V, X, or XVII) produced an immediate and dose-dependent inhibition of locomotor activity. On the other hand, AVT stimulated activity when administered ip to juvenile or adult female bullfrogs, but did not influence activity in juvenile or adult males. The minimum effective dose of AVT, when injected directly into the brain of tadpoles, was 100-fold less than that observed when injected ip, suggesting a central nervous system site of action for this peptide. A vasopressin receptor antagonist (d(CH2)5[Tyr(Me)2]AVP administered ip or icv) significantly increased locomotor activity in tadpoles, compared to controls. Oxytocin, vasopressin, and AVP4-9 inhibited activity in tadpoles while mesotocin, des Gly(NH2)AVP, and pressinoic acid had no significant effect. Injection of PGF2 alpha also significantly decreased activity levels in tadpoles. However, pretreatment of tadpoles with indomethacin, a prostaglandin synthesis inhibitor, did not prevent the behavioral effects of AVT, suggesting that prostaglandin synthesis is not required for this response. In summary, AVT influenced locomotor activity in bullfrog tadpoles and female frogs. This effect shifted during development from an inhibitory action in tadpoles to a stimulatory effect in metamorphosed female frogs. The effect of AVT on juvenile and adult frog locomotion was sexually dimorphic, as this peptide altered female behavior but not male behavior.
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PMID:Effect of vasotocin on locomotor activity in bullfrogs varies with developmental stage and sex. 204 91


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