Thesis (Ph. D.)--Oregon State University, 2007. / Printout. Includes bibliographical references. Also available on the World Wide Web.

Zugl.: Zürich, Univ., Diss., 2008

Thesis (M.S.)--University of Wisconsin--Madison, 1982. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 48-51).

Thesis--University of Wisconsin--Madison. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

The oxytocic activity of the neurointermediate lobe of the pituitary of the elasraobranch, Squalus acanthias (Pacific variety), was studied with chromatographic and pharmacological techniques, in an effort to determine whether the activity was due to a single or to a number of similar neurohypophysial principles. Neurointermediate lobes (NIL's) were dissected from live specimens of Squalus acanthias caught on the Pacific coast of Canada during 1966-67. The tissues were acetone dried and extracted in 0.25% acetic acid in saline. The extracts were assayed on the isolated rat uterus for their oxytocic activity, both in the presence and absence of magnesium ions, and in one case for rabbit milk ejection activity and antidiuretic activity in the anaesthetized rat. The ratio of milk ejection:rat uterus: rat antidiuretic activity was 2.6:1:0.046 which was in excellent agreement with the observations of previous investigators. However, this ratio contrasts with the 1:1:1 ratio of International standard ox posterior pituitary powder and indicates the presence of an elasmobranch oxytocic principle or principles similar to but not identical with oxytocin. This result was confirmed by the potentiation of the elasmobranch oxytocic activity in the presence of magnesium ions, a property typical of oxytocin analogues but not of oxytocin itself. The elasmobranch extracts showed a 1.2 – 3.2 fold range of magnesium potentiations and agreed with the values published by Sawyer (1965b). However, no extract in the 16 samples assayed showed sufficient potentiation to indicate the presence of significant amounts of a highly potentiated peptide (6 - 10 fold potentiation) such as postulated by Heller and Roy (1964) or Acher, Chauvet, Chauvet and Crepy (1965). Paper chromatography of the oxytocic activity using butanol/ acetic acid (glacial)/water (4:1:5) solvent system, was extended from the low oxytocic activity load levels utilized by Perks (i960) to loads beyond those used by Heller and Roy (196k) in which they detected two separable oxytocic activity peaks. Paper chromatography of our crude extracts at loads of 30 - 500 milli-units (without Mg⁺⁺), showed only one chromatographic peak, with an Rf approximating 0.4 - 0.5, which ran slightly slower than synthetic oxytocin Rf 0.5 - 0.6. No magnesium potentiation greater than a 3-fold potentiation could be detected in any regions of these chromatograms. Crude extracts ranging from 1148 to 7356 milliunits oxytocic activity were partially purified by the mild procedure of gel filtration on Sephadex G-15 in order that higher loads of oxytocic activity could be chrornatogrammed without artifacts due to overloading with protein. Despite the chromatography of levels of oxytocic activity higher than any previously.reported, the oxytocic activity never resolved into more than one chromatographic peak, and no region of the chromatograms potentiated beyond 3.4 when assayed with magnesium. The study of 16 different extracts from the neurointermediate lobes of Squalus acanthias (Pacific variety) gave no evidence for any large content of an oxytocic neurohypophysial principle potentiated 6-10 fold by magnesium ions. The use of paper chromatography techniques identical to those used by Heller and Roy (1964) failed to resolve more than one oxytocic principle, despite the use of oxytocic activity loads beyond those used by these authors. It is concluded that in the case of certain extracts of the oxytocic moiety of the Squalus acanthias (Pacific variety) neurointermediate lobe, there is no evidence for the presence of more than one oxytocic neurohypophysial principle. / Science, Faculty of / Zoology, Department of / Graduate

Oxytocin (OXT), a neuropeptide synthesized in the paraventricular nucleus (PVN) of the hypothalamus, functions to increase the precedence of social stimuli and promote the development of a wide range of social behaviors. However, whether OXT has a predicting role in social reward has yet to be examined. In this study, we developed a genetically encoded, scalable OXT sensor named OXTR-iTango2 and applied this technique to define the role of OXT in learned social behaviors. OXTR-iTango2 enables the combination of light- and ligand- dependent gene expression both in vitro and in vivo neural systems. In order to study the predictive role of OXT during expected socially rewarding experiences, we first conditioned animals to a social environment, and then selectively labeled OXT-sensitive ventral tegmental area dopamine (VTA-DA) neurons when animals encountered a conditioned stimulus that stood to predict a familiar social reward. Recurrent exposure to the same social stimulus normally lowered the degree of social interaction, but this reduced interaction was not observed when OXT-sensitive DA neurons were optogenetically inhibited. Thus, our findings support the notion that OXT plays a role beyond promoting social interactions, leading for a new proposed hypothesis that OXT mediation also leads to active avoidance of mundane social interactions. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2020. / FAU Electronic Theses and Dissertations Collection

Thesis (Ph. D.)--University of Washington, 1997. / Vita. Includes bibliographical references (leaves [122]-139).

No description available.

No description available.

The synthesis of seventeen novel conformationally constrained analogues of the neurohypophyseal peptide hormone oxytocin is described. Synthesis of the peptides was accomplished using solid-phase synthesis techniques on either Merrifield or p-methyl-benzhydrylamine resin. Cleavage of peptides from the solid support and deprotection were carried out by either ammonolysis followed by treatment with sodium in liquid ammonia or anhydrous HF. Disulfide formation was accomplished by treatment of the deprotected peptide with aqueous potassium ferricyanide. Purification of the peptide analogues involved a combination of either partition and/or size exclusion chromatography followed by reverse-phase high-performance liquid chromatography. Several conformationally constrained unnatural amino acids were incorporated into the synthetic peptides. Two were prepared and incorporated as a mixture of isomers and the resulting peptides were separated and purified by HPLC. The types of analogues prepared fall into three categories: analogues incorporating conformational restrictions in positions 1 and 2; bicyclic oxytocin peptides; oxytocin antagonists with changes at the Asn⁵ residue. The peptides with conformational restrictions at position 1 or 2 are: [Tic²]OT, [DTic²]OT, [DTic²,Thr⁴]OT, [β-MePhe²]OT, [ΔPhe²]OT, [Cys(CH₂)₅¹,Phe²,Thr⁴,Orn⁸]OT and [Pen¹,DPhe²,Thr⁴,Orn⁸]OT. Bicyclic peptide analogues and their monocyclic precursors include: [Mpa¹,Lys⁴,Glu⁵]OT, [Mpa¹,Lys⁴,Glu⁵]OT, [Mpa¹,Glu⁴,Lys⁸]OT, and [Mpa¹,Glu⁴,Lys⁸]OT. Antagonists with changes in the Asn⁵ residue are: [Pen¹,DPhe²,Thr⁴,Thr⁵,Orn⁸]OT; [Pen¹,DPhe²,Thr⁴,Leu⁵,Orn⁸]OT; [Pen¹,DPhe²,Thr⁴,Asp⁵,Orn⁸]OT; and [Pen¹,DPhe²,Thr⁴,Tyr⁵,Orn⁸]OT. Biological assays of these analogues for oxytocic activity in the rat uterus model have shown one of the β-MePhe²-containing peptides, [L-threo-β-MePhe²]OT, to be a very potent agonist and one bicyclic, [Mpa¹,Glu⁴,Lys⁸]OT to be an extremely potent oxytocin antagonist. Initial biophysical investigations employing 250 MHz nuclear magnetic resonance spectroscopy were also undertaken in order to determine possible solution conformations of these peptide analogues.