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)

A sensitive and precise method for assaying the water permeability response evoked by neurohypophyseal hormones and their synthetic analogues on the isolated urinary bladder of the toad (Bufo marinus L.) is described. The method permits detection of 8-arginine-vasotocin at concentrations as low as 10(-12)M. This sensitivity, not achieved heretofore with this tissue, results largely from minimizing interference of inhibitory substances by means of an "in vitro circulation assembly." The precision of the method derives from a direct comparison between the cumulative dose-response curve of an agonist of unknown potency acting on one hemibladder and that of a reference compound acting on the contralateral hemibladder. Crystalline deamino-oxytocin is used as the reference standard in this assay. The intrinsic activity of 2-(O-methyltyrosine)-oxytocin, as defined by the maximal response, is 12% lower than that of deamino-oxytocin. All other hormonal peptides investigated have the same intrinsic activity as deamino-oxytocin, even 5-valine-oxytocin, in spite of its extremely low affinity. A comparison of the potencies of 8-arginine-vasotocin vs. 8-arginine-vasopressin, 8-ornithine-vasotocin vs. 8-ornithine-vasopressin, 8-alanine-oxytocin vs. 8-alanine-oxypressin, and deamino-8-alanine-oxytocin vs. deamino-8-alanine-oxypressin suggests that an isoleucine residue in position 3 imparts a higher specificity for binding of the hormonal peptide molecule to the bladder receptor than a phenylalanine residue in this locus.
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PMID:A sensitive hydroosmotic toad bladder assay. Affinity and intrinsic activity of neurohypophyseal peptides. 569 11

Specific SRIF(1-14) fragments were synthetized on resin using conventional procedures. Rabbits received subcutaneously peptidyl resins in complete Freund adjuvant emulsion. The presence of antibodies was assessed by immunocytochemical and radioimmunological assays. 1. Peptidyl resins lead to antibodies production; their specificity depends on sequence and molecular configuration of the peptide on the resin. Anti-resin antibodies were not detected. 2. In the brain, SRIF(1-4) (in rat) and SRIF(10-13) (in garden-dormouse) can be demonstrated in neurophysins--positive cells of both paraventricular and supraoptic nucleus, but never in hypothalamic or extrahypothalamic SRIF(1-14)--positive neurophysin negative cells. 3. Endocrine cells of pancreatic islets contain SRIF(6-9) (in man) or SRIF(10-13) (in rat, mouse, garden-dormouse); generally, these cells are not detected by SRIF(1-14) anti-serum. Moreover, SRIF(10-13) positive cells are also detected by specific glucagon antibodies. However, it cannot be concluded that SRIF(10-13) antibodies reveal the common Thr-Phe-Thr-Ser fragment in the entire glucagon molecule. It is postulated that antibodies to several SRIF tetrapeptides reveal molecular fragments provided by the functional cleavage of an hypothetical prohormone or by the inactivation of SRIF(1-14) molecule in target cells.
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PMID:[Preparation of antisera against some sequences of somatostatin synthetized on resin. Application to the immunological detection of somatostatin systems: preliminary results (author's transl)]. 612 35

Three different antisera to the molluscan neuropeptide Phe-Met-Arg-Phe-amide (FMRFamide) and two different antisera to the fragment RFamide were used to stain sections or whole mounts of the hydrozoan medusa Polyorchis penicillatus. All antisera stained the same neuronal structures. Strong immunoreactivity was found in neurons of the ectodermal nerve nets of the manubrium and tentacles, in neurons of the sensory epithelium, and in neurons at the periphery of the sphincter muscle. Strong immunoreactivity was also present in processes and perikarya of the whole outer nerve ring, in the ocellar nerves, and in nerve cells lying at the periphery of the ocellus. The inner nerve ring contained a moderate number of immunoreactive processes and perikarya, which were distinct from the swimming motor neurons. In contrast to the situation in the hydrozoan polyp Hydra attenuata, no immunoreactivity was found with several antisera to oxytocin/vasopressin and bombesin/gastrin-releasing peptide. The morphology and location of most FMRFamide-immunoreactive neurons in Polyorchis coincides with two identified neuronal systems, which have been recently discovered from neurophysiological studies.
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PMID:FMRFamide immunoreactivity in the nervous system of the medusa Polyorchis penicillatus. 615 69

The hypothalamo-neurohypophysial system, containing the hormones oxytocin (OT) and vasopressin (VP) and their associated carrier proteins, the neurophysins (NPS), has been the subject of extensive investigation for more than 40 years. This system has been reinvestigated during the last decade by application of immunocytochemical methods employing the rabbit antisera to the hormones and NPS. In this study we describe the preparation and characterization of a monoclonal antibody to VP and its application in immunohistochemistry. The antibody did not cross-react with OT or arginine vasotocin (AVT). Its antigenic determinants as characterized by absorption with various VP analogs included two aromatic amino acids: Phe in position 3, and to a lesser extent Tyr in 2. Tissue fixation with formaldehyde resulted in inadequate immunostaining as compared to glutaraldehyde, most likely due to interference with the aromatic amino acid determinants by the former fixative.
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PMID:A monoclonal antibody to vasopressin: preparation, characterization, and application in immunocytochemistry. 618 60

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

Despite the absence of vasopressin, Brattleboro homozygous (DI) rats concentrate their urine to hypertonic levels when deprived of drinking water for 24 h. Glomerular filtration rate (GFR) falls concurrently and might contribute to the increased concentrating ability. The present studies concerned the time course of the changes in concentrating ability and GFR during the early hours of dehydration. Experiments were performed in 10 chronically catheterized conscious DI rats in the normally hydrated control state and during 3 h of fluid deprivation. Urine osmolality (Uosmol) increased from 97 +/- 6 (SE) to 325 +/- 11 mosmol/kg H2O at 3 h. Averaged over the 3 h, neither GFR nor effective renal blood flow changed significantly (103 +/- 2 and 106 +/- 4% of control, respectively). Fractional excretion of sodium (FENa) rose markedly from 0.3 +/- 0.1 to 1.3 +/- 0.1% at its peak. Clearly, a fall in GFR cannot explain the rise in Uosmol during the first 3 h. Plasma oxytocin (OT) increased from 5.6 +/- 0.8 to 36.4 +/- 4.5 pg/ml after 3 h of dehydration. In additional experiments, d(CH2)5-D-Phe-VAVP, an antidiuretic antagonist (anti-ADH), was administered to eight DI rats after 3-h dehydration. Control, 3-h dehydration, and post-anti-ADH values were, respectively: for Uosmol, 102 +/- 7, 347 +/- 14, 145 +/- 11 mosmol/kg H2O; for GFR, 1,003 +/- 43, 1,042 +/- 59, 866 +/- 54 microliter X min-1 X 100 g body wt-1; for FENa, 0.4 +/- 0.1, 1.4 +/- 0.1, 0.5 +/- 0.1%. The decreases following anti-ADH were all statistically significant. We conclude that OT is released during the early hours of dehydration in the DI rat and has at least three renal effects. It causes a natriuresis, it maintains renal hemodynamics and GFR during the volume contraction, and it elicits a weak antidiuretic response.
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PMID:Antidiuretic effect of endogenous oxytocin in dehydrated Brattleboro homozygous rats. 647 23

The structural interdependence between neurophysin (NP) self-association and ligand binding surfaces has been studied by analytical affinity chromatography of several NP sequence variants and derivatives on Met-Tyr-Phe-aminobutyl-agarose and bovine NP-II Sepharose. Elutions of radiolabeled NP's from both matrices show that hybrid dimers can form between major bovine NP's (I and II, or VLDV- and MSEL-NP's, respectively), as well as between human and bovine NP's, with affinities close to that for homologous dimer formation. Such evidence supports the view that the region of NP involved in NP-NP contact is composed primarily of conserved structural elements of the protein. NP antibodies which recognize surfaces close to or in the NP-NP contact region have been detected by their effects on bovine NP-II elution on NP-II Sepharose. Elutions of [3-nitro-Tyr 49] BNP-II from Met-Tyr-Phe-aminobutyl-agarose showed that nitration has little effect on the chromatographic properties of NP-II. This evidence substantiates previous arguments (Angal, S. & Chaiken, I.M. (1982) Biochemistry 21, 1574-1580) that the chromatographic behavior of native NP's on the affinity matrices is an expression of the interdependence of NP self-association and ligand binding surfaces and not due to bivalent peptide binding by NP monomer. The affinity chromatographic properties of NP derivatives, including bovine NP-II photolabeled in the ligand binding site and tryptic fragments of bovine NP-I (NP-I-(9-93) and [des 19-20] NP-I-(9-93)), support the view that the surfaces for ligand binding and NP-NP contact are conformationally linked. The data argue that conformational changes that ensue upon noncovalent ligand binding and lead to enhanced NP self-association cannot occur favorably with the protein modified by either covalent ligand attachment or limited amino-terminal proteolysis.
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PMID:Cooperative interactions in neurophysin-neuropeptide hormone complexes. Analytical affinity chromatography of native and covalently-modified neurophysins. 650 Aug 6

Nacartocin, a synthetic analogue of oxytocin, [2-L-p-phenylalanine]deamino-6-carba-oxytocin has a specific natriuretic effect in cats. The doses of 0.05-10 micrograms/kg b.w. (0.05-10 nmols/kg) of Nacartocin applied i.v. caused a several fold increase in the excretion of sodium, while the excretion of kalium was only slightly enhanced.
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PMID:Natriuretic properties of [2-p-ethylphenylalanine] deamino-6-carba-oxytocin (Nacartocin) in cats. 654 87

As part of a program in which we are attempting (a) to delineate the structural features at positions 1-9 in our previously reported antidiuretic antagonists required for antidiuretic antagonism and (b) to obtain analogues with enhanced antiantidiuretic potency and/or selectivity, we have synthesized 14 new analogues of the antidiuretic antagonist [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid),2-D-phenylalanine,4-valine]arginine-vasopressin [d-(CH2)5-D-Phe2VAVP), in which the valine residue at position 4 was replaced by the following L-amino acids and glycine: Ile, Abu, Thr, Ala, Gln, Lys, Cha, Nle, Nva, Phe, Leu, Gly, Tyr, and Pro. These analogues are 1, d-(CH2)5-D-Phe2,Ile4AVP; 2, d(CH2)5-D-Phe2,Abu4AVP; 3, d(CH2)5-D-Phe2,Thr4AVP; 4, d(CH2)5-D-Phe2,Ala4AVP;5, d(CH2)5-D-Phe2AVP; 6, d(CH2)5-D-Phe2,Lys4AVP; 7, d(CH2)5-D-Phe2,Cha4AVP; 8, d(CH2)5-D-Phe2,Nle4AVP; 9, d(CH2)5-D-Phe2,Nva4AVP; 10, d(CH2)5-D-Phe2,Phe4AVP; 11, d(CH2)5-D-Phe2,Leu4AVP; 12, d(CH2)5-D-Phe2,Gly4AVP; 13, d(CH2)5-D-Phe2,Tyr4AVP; 14, d(CH2)5-D-Phe2,Pro4AVP. The protected intermediates required for the synthesis of all of these peptides were prepared by the solid-phase method and cleaved from the resin by ammonolysis. Following deblocking with Na in NH3 and oxidizing with K3[Fe(CN)6], each peptide was purified on Sephadex G-15 in a two-step procedure using 50% HOAc and 0.2 M HOAc as eluants. Analogues 1-14 were tested for agonistic and antagonistic activities by antidiuretic, vasopressor, and oxytocic assays in rats. Analogues 1, 2, and 4-6 exhibit no detectable antidiuretic agonistic activity. All analogues, with the exception of the Pro4-containing analogue, are antidiuretic antagonists. Their antiantidiuretic pA2 values are as follows: 1, 8.24 +/- 0.08; 2, 7.96 +/- 0.07; 3, 7.62 +/- 0.09; 4, 7.52 +/- 0.03; 5, 7.21 +/- 0.07; 6, 7.22 +/- 0.12; 7, 7.19 +/- 0.08; 8, 7.12 +/- 0.09; 9, 6.99 +/- 0.06; 10, 6.07 +/- 0.11; 11, 6.07 +/- 0.11; 12, 5.85 +/- 0.05; 13, approximately 5.57; 14, a weak agonist (0.004 U/mg). Analogues 1-14 also antagonize the vascular responses to arginine-vasopressin (AVP) and the in vitro oxytocic responses to oxytocin. Analogues 1, 2, 3, and 5 have also been shown to antagonize the in vivo oxytocic responses to oxytocin. Five of these analogues (1, 2, 3, 6, and 7) exhibit enhanced antiantidiuretic/antivasopressor selectivity. d(CH2)5-D-Phe2,Lys4AVP and other position-4 analogues with side-chain functional groups may be useful covalent ligands with which to probe the structural characteristics of AVP renal and vascular receptors. With an antiantidiuretic "effective dose" of 0.46 +/- 0.07 nmol/kg and a pA2 value of 8.24 +/- 0.08, d(CH2)5-D-Phe2,Ile4AVP (1) appears to be the most potent antidiuretic antagonist reported to date.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Potent antagonists of the antidiuretic responses to arginine-vasopressin based on modifications of [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid),2-D- phenylalanine,4-valine]arginine-vasopressin at position 4. 663 16

Mesotocin ([Ile8]-oxytocin), lysipressin ([ Lys8]-vasopressin) and phenypressin ([Phe8]-vasopressin) have been identified in the western gray kangaroo (Macropus fuliginosus) as well as four other macropodids. Lysipressin and phenypressin, which differ by the amino acids in positions 2 (Tyr/Phe) and 8 (Lys/Arg) are likely products of two separate vasopressin-like genes. It is assumed that arginine vasopressin found in most mammals is the product of two identical genes which can be revealed in some species by differential mutations as seen usually in marsupials. The duality can also be revealed by differential mutations in another domain of the precursors, such as the neurophysin (MSEL-neurophysin), as observed in the ox.
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PMID:A multigene family for the vasopressin-like hormones? Identification of mesotocin, lysipressin and phenypressin in Australian macropods. 663 61


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