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Regulation of photoperiodic prolactin secretion the possible roles of the pars tuberalis and tachykinins /Adetoye, Mercy A. January 2009 (has links)
Thesis (M.S.)--University of Wyoming, 2009. / Title from PDF title page (viewed on July 22, 2010). Includes bibliographical references (p. 74-91).
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Role of tachykinin receptors in emesis control in suncus murinus (house musk shrew). / CUHK electronic theses & dissertations collectionJanuary 2007 (has links)
Capsaicin (1.3 mumol/kg, i.v.) and resiniferatoxin (48 nmol/kg, i.v.) failed to induce plasma extravasation in Suncus murinus (P>0.05). But SP (20 nmol/kg, i.v.) was able to induce salivation, and plasma extravasation in the bladder and the trachea significantly (P<0.05). NK1 receptor antagonists CP-99,994, R116301 (ID50 = 1.2 mumol/kg), and R115614 (ID50 = 1.8 mumol/kg) significantly reduced plasma leakage in the bladder (P<0.05), but not the trachea (P>0.05). R116301 (ID50 = 0.7 mumol/kg) and R115614 (ID50 = 1.2 mumol/kg) were able to inhibit the salivation response significantly (P<0.05). / R116301 and R115614 significantly reduced emesis induced by resiniferatoxin, motion, copper sulphate, and cisplatin (P<0.05), in the dose range between 23-70 mumol/kg, s.c. Both antagonists (100-300 nmol, i.c.v.) were also able to reduce cisplatin-induced emesis significantly (P<0.05), but only R116301 (10-300 nmol, i.c.v.) was able to significantly inhibit emesis induced by nicotine and copper sulphate (P<0.05). / The development of tachyldnin NK1 receptor antagonist aprepitant as an effective anti-emetic drug illustrates the importance of NK1 receptors in the emetic reflex. However, the exact anti-emetic mechanism of action is still unknown. The primary aim of the study was to investigate the relative contribution of centrally versus peripherally located NK1 receptors in the emetic reflex in Suncus murinus. The study also investigated the potential contribution of NK2 and NK3 receptors in emesis control. / The present studies demonstrated that R116301 and R115614 exhibited anti-emetic properties against various drugs, motion, and tachykinin receptor agonists. The studies also imply the existence of the classical SP subsite and the septide subsite of the NK1 receptors that are involved in the emetic reflex of Suncus murinus, which suggests that NK1 receptor antagonists that can block both subsites could become effective anti-emetic drugs. The present studies also demonstrated that both NK2 and NK3 receptors maybe involved in emesis control. It is possible that dual NK1/NK2 receptor antagonists or triple NK 1/NK2/NK3 receptor antagonists may have clinical potential as anti-emetic drugs besides the clinically used NK1 receptor antagonists. / The rank order of potency (based on pEC50 values) of tachykinin receptor agonists to contract Suncus murinus ileum was as follow: [Sar9Met(O2)11] substance P (SP) (8.1) > septide (7.9) (both NK1 receptor agonists) > neurokinin A (NKA) (7.7) > SP (7.6) > GR 64349 (NK2 receptor agonist) (7.0). For the NK1 receptor antagonists, the rank order of potency (based on pKB/pA2 values) to inhibit ileal contraction was: R116301 (7.8-8.2) ≈ R115614 (7.7-8.3) > CP-99,994 (6.4-7.3) against various NK1 receptor agonists. Furthermore, NK2 receptor antagonist saredutant (pA2 = 7.3) competitively antagonised GR 64349-induced ileal contraction. / When injected intracerebroventricularly, SP (100 nmol), septide, [Sar 9Met(O2)11] SP, NKA (all at 30 nmol), GR 64349 (10 and 30 nmol), and senktide (NK3 receptor agonist) (3-30 nmol) significantly induced emesis in Suncus murinus (P<0.05). They were also effective in inducing locomotor hyperactivity, ano-genital grooming, circling, face washing, hindlimb licking, scratching, and straub tail (3-30 nmol, P<0.05). R116301 and R115614 (both at 3 and 10 mumol/kg, s.c.) significantly antagonised some of the actions of the agonists including emesis, locomotor hyperactivity, ano-genital grooming, licking, scratching, and straub tail (P<0.05). Saredutant and NK3 receptor antagonist osanetant (both at 30 mumol/kg, s.c.) attenuated emesis induced by GR 64349 and senktide respectively (P<0.05). Saredutant (30 mumol/kg, s.c.) was also able to inhibit GR 64349-induced face washing and scratching, while osanetant (30 mumol/kg, s.c.) also significantly attenuated senktide-induced straub tail (P<0.05). / Cheng, Ho Man Frankie. / "September 2007." / Adviser: John A. Rudd. / Source: Dissertation Abstracts International, Volume: 69-08, Section: B, page: 4691. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (p. 194-223). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract in English and Chinese. / School code: 1307.
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Functional neuroanatomy of tachykinins in brainstem autonomic regulationMakeham, John M. January 2006 (has links)
Thesis (Ph. D.)--University of Sydney, 2007. / Title from title screen (viewed 1 November 2007). Submitted in fulfilment of the requirements for the degree of Doctor of Philosophy to the Discipline of Physiology, Faculty of Medicine. Degree awarded 2007 ; thesis submitted 2006. Bibliography: leaves 239-284. Also issued in print.
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Contribution of neurokinin 3 receptor signaling to systemic vasopressin and oxytocin releaseHaley, Gwendolen E. January 2008 (has links)
Thesis (Ph.D.)--University of Wyoming, 2008. / Title from PDF title page (viewed on June 24, 2009). Includes bibliographical references (p. 158-174).
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Expression and characterization of the human neurokinin 1 receptor from Escherichia coliBane, Steven Edward. January 2007 (has links)
Thesis (Ph.D.)--University of Delaware, 2007. / Principal faculty advisor: Anne Skaja Robinson, Dept. of Chemical Engineering. Includes bibliographical references.
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Molecular genetic analysis of the neurokinin B (TAC3) and neurokinin B receptor (TAC3) genes as candidates for pre-eclampsiaCarelse Tofa, Kashefa 12 1900 (has links)
Thesis (MSc)--Stellenbosch University, 2004. / ENGLISH ABSTRACT: Hypertensive conditions of pregnancy, such as pre-eclampsia, are the principal direct
cause of maternal morbidity and mortality and affect up to 10% of first pregnancies
worldwide. The placenta is vital in the pathogenesis of pre-eclampsia since the
condition only occurs in the presence of placental tissue and the only cure is delivery
of the placenta and the fetus. It has been hypothesised that the placenta may be the
source of a circulating factor(s), which transports freely in the maternal system,
resulting in the multi-systemic and immunological responses that are characteristic of
pre-eclampsia. Among the potential "circulating" candidates currently being
investigated worldwide, is the tachykinin member, neurokinin B (NKB).
The aim of this project was to use a novel approach and investigate the role of
Neurokinin B in pre-eclampsia on a genetic level. This would be achieved by
bioinformatie characterisation of the neurokinin B (TAC3) and neurokinin B receptor
(TACR3) genes. Samples from thirty pre-eclampsia patients (of whom 10 also had
abruptio placentae) and twenty control individuals were used for mutation detection
analysis involving Multiphor gel electrophoresis and automated sequencing.
Three sequence variants were identified in the TAC3 gene and include: (i) 5' UTR
variant (-25 c-t); (ii) intronic variant IVS3-53 (t-g) and (iii) 3' UTR variant exon 7
(479, t-c). Only the -25 c-t variant had been reported before (SNP database). A
further two variants were identified in the TACR3 gene: (i) exon 3 variant (nt 857, a-t)
and (ii) 3' UTR variant, amplicon 5b (nt 1471, t-c), of which the latter had previously
been reported in the SNP database. In the analysis of allele and genotype frequencies,
only variant homozygosity for TAC3 -25 c-t could be associated with increased risk
of pre-eclampsia (RR 3.33, p=0.03). Follow-up work will include extended
genotyping in further stratified and larger patient cohorts and transfection studies to
assess splicing potential and functional consequences of the mutant alleles.
These data represent the first documented mutation screen of the TAC3 and TACR3
genes and report novel variants in patients with pre-eclampsia. This study contributes
to the knowledge of neurokinin B as a circulatory molecule and confirms the
heterogeneity of pre-eclampsia. / AFRIKAANSE OPSOMMING: Die belangrikste direkte oorsaak van moedersterftes is hipertensiewe toestande in
swangerskap, insluitende pre-eklampsie. Hierdie toestande kompliseer wêreldwyd
10% van alle swangerskappe. Die plasenta is kardinaal in die ontwikkeling van die
siekte aangesien dit slegs voorkom terwyl die plasenta in-situ is en die simptome
opklaar na verlossing van die plasenta. 'n Moontlike hipotese is dat die plasenta 'n
sirkulerende agens afskei wat in die moederlike sisteem beland en die uiteenlopende
multi-sistemiese simptome en tekens van die siekte veroorsaak, asook aktivering van
die immuunsisteem. Een van die moontlike kandidate wat tans wêreldwyd ondersoek
word as moontlike sirkulerende agens, is Neurokinien B (NKB), 'n lid van die
Tachikinien familie.
Die unieke benadering van hierdie projek was om die rol van Neurokinien B in pre-eklampsie
te ondersoek op 'n genetiese grondslag. Dit is bereik deur bio-informatiewe
karakterisering van die neurokinien B (TAC3) en neurokinien B reseptor (TACR3) en
deur mutasie sifting op DNA monsters van 30 pasiënte met pre-eklampsie (waarvan
10 ook abruptio placentae gehad het) en twintig kontrole individue met behulp van
Multiphor gel elektroforese en ge-outomatiseerde volgorde bepaling.
Drie volgorde variasies is geïdentifiseer in die TAC3 geen en sluit in: (i) 5' UTR
variant (-25 c-t); (ii) introniese variant IVS3-53 (t-g) en (iii) 3' UTR variant in ekson
7 (479, t-e). Slegs die -25 c-t variasie is voorheen raporteer (SNP databasis). Nog
twee variante is ook gevind in die TACR3 geen: (i) ekson 3 variant (nt 857, a-t) en (ii)
3' UTR variant, amplikon 5b (nt 1471, t-e); hierdie laaste een is al in die SNP
databasis raporteer. In 'n analise van genotipe en allele frekwensies is slegs
homosigositeit vir variant TAC3 -25 c-t geassosieër met 'n verhoogde risiko vir preeklampsie
(RR 3.33, p=0.03). Verdere werk sal nou fokus op die genotipering van
groter en gestratifiseerde pasiënt kohorte en transfeksie studies om splitsing potensiaal
en funksionele gevolge van mutante allele te ondersoek.
Hierdie data is die eerste gedokumenteerde mutasie sifting van die TAC3 en TACR3
gene en verslag word gelewer van unieke variasies in pasiënte met pre-eklampsie.
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Synthesis and biological activities of tachykinin and opioid-related compounds, synthesis of unusual amino acids, and the investigations into the smooth muscle pharmacology of tachykinins.Landis, Geoffrey Carrothers. January 1989 (has links)
Eight cyclic analogues of Substance P were made in order to investigate the conformation of the C-terminal end of the peptide. These analogues were designed to test three literature models describing the active conformation of substance P. Although the potencies of the analogues were low (in the micromolar range), our results support Cotrait's and Hospital's model (1986). Several substance P antagonists were synthesized. These compounds did not demonstrate agonistic activity nor anatagonistic activity. The tryptophan side chain is contributing to the antagonistic activity of these analogues, and not just the chirality of the α-carbon. Highly potent and selective photoaffinity ligands of H-Tyr-D-Pen-Gly-Phe-D-Pen-OH (DPDPE) and D-Phe-Cys-Tyr-D-Trp-Lys-Thr-Pen-Thr-NH₂ (CTP) were synthesized. These compounds will be useful in the isolation of δ and μ opioid receptors. Several new amino acids designed and synthesized to contain both the natural amino acid side chain and a thiol group which can be used to make disulfide constraints. The racemic amino acids made were as follows: (1) 2-amino-4-methyl-2- [(p-methylbenzyl)thiomethyl] pentanoic acid; (2) 2-amino-2- [(p-methylbenzyl)thiomethyl] -3-phenylpropanoic acid; (3) 2-amino-e- [(p-methylbenzyl)thio] pentanoic acid; and (4) 2-amino-3- [(p-methylbenzyl)-thio] -3-phenyl-pentanoic acid. These amino acids will be useful in the conformational restriction of peptides. To investigate the δ-opioid receptor conformation proposed for DPDPE by Hruby et al. (1988) and the μ-opioid receptor conformation proposed for Tyr-c [Abu₂,Gly,Phe,Leu] by Mierke et al. (1988), constrained phenylalanine amino acids were incorporated into H-Try-D-Pen-Gly-Phe-D-Pen-OH (DPDPE) in the four position. Our results indicate that these models are correct. And in an investigation into the physical-chemical properties of the delta opioid receptor, our results suggest that the δ receptor topochemical site for the Phe⁴ residue contains a partial positive charge on its surface and has specific steric requirements.
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The role of neuropeptides in inflammatory disease / by Andrzej Wozniak.Wozniak, Andrzej, 1956- January 1992 (has links)
Copies of author's previously published articles inserted. / Amendments (2 leaves) in front cover pocket. / Bibliography: leaves 227-259. / xiii, 259 leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Examines the contribution of tachykinins, in particular Substance P (SP), to the processes of inflammation. / Thesis (Ph.D.)--University of Adelaide, Dept. of Medicine, 1993
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Characterization of Responses to Neurokinin a in the Isolated Perfused Guinea Pig HeartHoover, Donald B., Chang, Yingzi, Hancock, John C. 01 January 1998 (has links)
Goals of this study were to identify and characterize effects of neurokinin A (NKA) in isolated guinea pig hearts. Bradycardia, augmentation of ventricular contractions, and reduction of perfusion pressure were prominent responses to bolus injections of NKA (0.25-25 nmol). NKA was more potent than substance P (SP) in causing bradycardia but did not differ in potency for lowering perfusion pressure. Doses of SP of 25 nmol or less decreased ventricular force, whereas 100 nmol caused a biphasic response. The percent decrease in heart rate produced by 25 nmol NKA was reduced from 58.0 ± 4.8 to 39.6 ± 3.5% in the presence of μM atropine (n = 5). The positive inotropic response to 25 nmol of NKA in spontaneously beating hearts was replaced by a negative inotropic response during pacing (22.5 ± 3.3% increase vs. 11.7 ± 1.7% decrease, n = 5). Reserpine pretreatment did not affect the positive inotropic response to NKA. Specific binding sites for (125)I-labeled NKA were localized to intracardiac ganglia and coronary arteries but not to myocardium. It was concluded that 1) negative chronotropic responses to NKA involve cholinergic and noncholinergic mechanisms, and 2) the positive inotropic response is an indirect action.
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Tumour biological factors characterizing metastasizing serotonin-producing ileocaecal carcinoids /Cunningham, Janet Lynn, January 2007 (has links)
Diss. (sammanfattning) Uppsala : Uppsala universitet, 2007. / Härtill 4 uppsatser.
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