The objective of this thesis was to test the hypothesis that the decreased effects of PGE$ sb2$ and PGF$ sb{2 alpha}$ on cerebral metabolism and vasculature in the newborn might result from a deficiency of brain EP and FP receptors, which may be downregulated by the relatively high brain levels of PGE$ sb2$ and PGF$ sb{2 alpha}.$ / This study revealed that the densities of EP and FP receptors and receptor-coupled second messengers in brain synaptosomes and microvessels were much lower in the newborn than in the adult pigs, also the relative distribution of EP receptor subtypes in brain synaptosomes and microvessels differed. For example, in brain synaptosomes, only EP$ sb3$ subtype was present in the newborn, and both EP$ sb2$ and EP$ sb3$ subtypes existed in the adult; EP$ sb1$ subtype was not found in the brain synaptosomes. In contrast, in brain microvessels, more than 80% of EP receptors were of EP$ sb1$ subtype with small amount of EP$ sb3$ subtype. No EP$ sb2$ subtype was detected in the brain microvessels. / In order to determine whether high levels of prostaglandin in the newborn downregulate EP and FP receptors, newborn pigs were treated with cyclooxygenase inhibitors, ibuprofen or indomethacin. The inhibition of prostaglandin synthesis in the newborn pigs significantly increased EP and FP receptor densities as well as receptor-coupled IP$ sb3$ and cAMP production in brain synaptosomes and microvessels of the newborn to levels found in the adult; this effect could be prevented by co-treatment of membranes with stable PG analogs. Vasoconstrictor effects of PGE$ sb2$ and PGF$ sb{2 alpha}$ on cerebral microvessels of the newborn were also increased. / These findings suggest that the relatively low EP and FP receptor densities in the newborn brain are caused by the high levels of prostaglandins and that these receptors and their functions can be upregulated by reducing prostagladin levels.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.39944 |
| Date | January 1995 |
| Creators | Li, Ding-You |
| Contributors | Varma, Daya R. (advisor), Chemtob, Sylvain (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Pharmacology & Therapeutics.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001495047, proquestno: NN12414, Theses scanned by UMI/ProQuest. |
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