Thesis (Doctoral)--Lunds universitet, 1990. / Includes bibliographical references.

No description available.

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Thesis (Ph. D.)--University of Virginia, 1997. / Includes bibliographical references (93-107). Also available online through Digital Dissertations.

Thesis (M.S.)--University of Oregon, 2006. / Includes bibliographical references (leaves 20-23). Also available online (PDF file) by a subscription to the set or by purchasing the individual file.

Thesis (M.S.)--University of Oregon, 2006. / Includes bibliographical references (leaves 20-23).

Thesis (doctoral)--Tallinn Technical University, 2001. / Includes bibliographical references (p. 59-64).

Prostanoid receptors (PG-Rs: prostaglandin D, E, F, prostacyclin and thromboxane receptors (DP, EP1-4, FP, IP and TP)) are known to mediate a diverse range of biological responses, such as cardiovascular homeostasis, nociception and reproduction, via binding to their respective ligands belonging to the five classes of prostanoids (PGs: class D, E, F, I and thromboxane). The majority of these findings were reported in mammals, and despite suggestive evidence provided by previous pharmacological and physiological studies in non-mammalian vertebrates, investigations on the mechanisms behind actions of PGs were impeded by the limited information on their receptors. In the present study, the full-length cDNAs of chicken (c-) and zebrafish (z-) prostanoid receptors – cEP3, cFPs, zEP1s and zFP – were identified from respective adult ovaries and their tissue distribution examined by RT-PCR. A novel middle-truncated splice variant, cFPb, which lacks 107 amino acids between transmembrane domains 4 and 6 but otherwise identical to cFPa was first identified. Three isoforms of zEP1 – zEP1a, zEP1b, zEP1c – were found, which might have subfunctionalized in their ligand binding and G protein coupling specificity, in addition to differential tissue distribution. Using various luciferase reporter systems (pGL3-CRE, pGL-NFAT-RE, pGL4-SRE), all the cloned receptors, except cFPb, were shown to potentially couple to intracellular cAMP, Ca2+, and/or MAPK signaling pathways. Owing to the proposed roles of PGs and its potential regulation by and/or on EGFR ligands and gonadotropins in mammals and chicken, genes involved in regulation of PG functions at various levels, including biosynthesis (COX1, COX2, mPGES1, mPGES2 and cPGES), availability (PGT) and signaling (cEPs and cFPs), were also characterized in granulosa cells during hen follicular development. Lastly, using our experimental data and systematic sequence retrieval from available databases, the PG receptor cascades from representative vertebrate species were pooled and analysed using phylogenetic analyses and synteny studies. Three putative clusters (IP-like, EP4-like and EP1-like cluster) were found in lamprey genome; meanwhile, only one PG-R-like cluster was identified from the Cephalochordate lancelet (amphioxus) genome. This concurs with the 1-2-4 rule proposed in first round/second round (1R/2R) whole genome duplication in which the missing lamprey cluster was presumably lost secondarily. With support from conserved orthologs-localization, the four PG-R paralogs (proto-EP4, proto-IP/EP2/DP, proto-TP/FP/EP1 & putative proto-EP3 genes) in the ancestral vertebrates might have further diversified via either localized- (e.g. EP2 and DP) or chromosomal segmental duplication (e.g. EP1, FP and TP) which resulted in the present array of vertebrate PGRs. Additional paralogs (e.g. EP1 and EP4) were identified from fishes, by which molecular dating coincide with and hint of their origins whence the ancient fishspecific whole genome duplication (3R) occurred ~350 million years ago. The present study offers the first glimpse and a better understanding of the roles of the PG-Rs and presents a higher resolution to the evolutionary history of each PG-R family member, consolidating that particular care has to be taken when studying non-mammalian PG-R functions in which some members are absent or present in multiples and propel the investigation of adaptational changes in the coding sequence during evolution of vertebrate PG-Rs. / published_or_final_version / Biological Sciences / Doctoral / Doctor of Philosophy

Vascular reactivity to vasopressin and phenylephrine is potentiated by constrictor prostanoids (CP) in normotensive female (F) but not male (M) rat aorta and CP function is estrogen-dependent. This study investigated the effects of estrogen on CP function and arterial blood pressure (MAP) during development of aortic coarctation-induced hypertension (HT). M and F rats, (15-18 wks.) in four groups: normotensive (NT), hypertensive (HT), ovariectomized (OVX), and OVX estrogen-replaced (OE), underwent abdominal aortic coarctation or sham surgery (NT). At 14 days, SQ 29,548 (SQ, Thromboxane A2 (TXA2) receptor antagonist) was given i.v. to the groups. In another experiment, rats received Ridogrel (TXA2 receptor antagonist+TXA2 synthase (TXS) inhibitor) or vehicle (methyl cellulose) daily, for 14 days. Thoracic aortae were analyzed for morphology, incubated in Kreb’s Henseleit Buffer (KHB) ± angiotensin II (ANG II), or underwent continuous pulsatile flow and pressure experiments (PFP) with KHB ± ANG II. Perfusate was analyzed for thromboxane B2 (TXB2) and prostaglandin F1α (PGF1α). RT-PCR and immunohistochemistry were performed for TXS. MAP was higher in F-HT than in M-HT after 14 days. SQ infusion reduced MAP substantially more in F-HT and OE-HT than in others. Ridogrel prevented increases in MAP in F/OE-HT rats, but not M/OVX-HT. Basal release of TXB2 and PGF1α increased to a greater extent in F-HT than in M-HT relative to their controls. ANG II-stimulated TXB2 and PGF1α release increased to a greater extent in F-HT than in M-HT. With or without ANG II, TXB2 production in HT during PFP increased with estrogen. PGF1α increased during PFP with estrogen, however not with ANG II. Pressurization resulted in less diameter change in F and OE-HT than in OVX-HT. Elastin increased with HT (inhibited by Ridogrel) in all but M. Collagen increased in HT with estrogen (inhibited by Ridogrel). Neither OVX-HT nor Ridogrel had any effect on morphology. Estrogen increased TXS with HT. Estrogen enhanced vascular CP and MAP in F-HT by increased expression of TXS and collagen density in the vasculature indicating that in aortic coarctation-induced HT, CP are upregulated by estrogen. Specific forms of HT in human beings may involve estrogen-induced vascular CP upregulation.