التفاصيل البيبلوغرافية
| العنوان: |
Studies upon the rat brain high-affinity choline transporter |
| المؤلفون: |
Ferguson, Stephen S. G. (Stephen Sean Gilbert) |
| مرشدي الرسالة: |
Collier, Brian (advisor) |
| بيانات النشر: |
McGill University, 1994. |
| سنة النشر: |
1994 |
| المجموعة: |
Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| مصطلحات موضوعية: |
Biology, Neuroscience. |
| جغرافية الموضوع: |
Doctor of Philosophy (Department of Pharmacology & Therapeutics.) |
| الوصف: |
Stereoanalogues of choline (R and S, $ alpha$- or $ beta$-methylcholine), hemicholinium-3 and choline mustard aziridinium ion were used as tools to investigate the structure and function of the high-affinity choline transporter. Three studies are presented. In the first, the methylcholines were used to study the stereoselective properties of the high-affinity choline transporter. The recognition of the methylcholines by the choline carrier was stereoselective, while their transport was stereospecific. This difference was interpreted as indicating that recognition and transport might represent distinct and dissociable components of the choline transporter. In a second study, the methylcholines were used to examine the stereoselectivity of ($ sp3$H) hemicholinium-3 binding to determine how this compared to the interaction of the methylcholines with choline uptake. The ability of these compounds to inhibit stereoselectively ($ sp3$H) hemicholinium-3 binding indicates that binding is to the substrate recognition site of the choline carrier. However, this site can assume two configurations, as defined by changes in its stereoselectivity for the methylcholines and affinity for hemicholinium-3. The conformational change of the substrate recognition site likely plays a role in initiating the substrate translocation process, since locking it in its high-affinity ($ sp3$H) hemicholinium-3 binding state reduces the rate of choline transport. In a third study, choline mustard aziridinium ion and hemicholinium-3 were used to investigate the mechanism by which activity regulates the velocity of choline transport. These studies indicate that the mechanism involves the changed activity of transport sites that are available to the mustard, and presumably choline, but not hemicholinium-3 prior to stimulation. In addition, two pools of basal transport sites have been identified on the basis of their sensitivity to choline mustard, as well as their ability to transport choline and b |
| Original Identifier: |
oai:collectionscanada.gc.ca:QMM.41586 |
| نوع الوثيقة: |
Electronic Thesis or Dissertation |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| العلاقة: |
alephsysno: 001397636; proquestno: NN94617; Theses scanned by UMI/ProQuest. |
| الإتاحة: |
http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=41586Test |
| حقوق: |
All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| رقم الانضمام: |
edsndl.LACETR.oai.collectionscanada.gc.ca.QMM.41586 |
| قاعدة البيانات: |
Networked Digital Library of Theses & Dissertations |
