Development of GABA(B) binding site distribution and pharmacology in rat brain.
dc.contributor.author | Turgeon, Sarah Macomb | |
dc.contributor.advisor | Albin, Roger | |
dc.date.accessioned | 2016-08-30T17:05:57Z | |
dc.date.available | 2016-08-30T17:05:57Z | |
dc.date.issued | 1994 | |
dc.identifier.uri | http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqm&rft_dat=xri:pqdiss:9423334 | |
dc.identifier.uri | https://hdl.handle.net/2027.42/129319 | |
dc.description.abstract | Quantitative receptor autoradiography with ($\sp3$H) GABA was used to characterize the distribution and pharmacological characteristics of GABA$\sb{\rm B}$ binding during the life span of the rat. During the first three postnatal weeks, GABA$\sb{\rm B}$ binding exhibits regionally specific peaks that coincide with synaptogenic and organizational events. Following this early postnatal peak, binding continues to decrease in all regions until the third postnatal month, at which point binding levels off. Saturation analyses reveal no dramatic changes in affinity or maximum binding from one week to two months but do reveal a decrease in affinity from two months to two years. These results suggest a developmental role for GABA$\sb{\rm B}$ binding sites during early postnatal life and the existence of subtypes of GABA$\sb{\rm B}$ binding sites with different affinities in aging brain. Pharmacological analyses of GABA$\sb{\rm B}$ binding also suggest the existence of multiple GABA$\sb{\rm B}$ binding site subtypes. Various competitive GABA$\sb{\rm B}$ ligands inhibit GABA$\sb{\rm B}$ binding in the adult brain with the same order of potency reported previously for ($\sp3$H) GABA binding to GABA$\sb{\rm B}$ binding sites. GTP-$\gamma$-S and GDP-$\beta$-S also inhibit GABA$\sb{\rm B}$ binding, verifying that the GABA$\sb{\rm B}$ receptor identified in this assay is a G-protein coupled receptor. However, zinc modulates binding in a regionally specific manner, enhancing binding at low concentrations and inhibiting binding at higher concentrations in some regions, but only inhibiting binding in other regions. In addition, the competitive antagonist CGP 35348 displaces binding from two separate sites, indicating that ($\sp3$H) GABA is binding to two GABA$\sb{\rm B}$ binding sites with different affinities. Comparisons of GABA$\sb{\rm B}$ binding site pharmacology reveal similarities between one week and two months and between two months and two years with the exception of zinc, which is more potent at one week than at two months. Therefore, whereas most available GABA$\sb{\rm B}$ ligands cannot distinguish between putative GABA$\sb{\rm B}$ binding site subtypes, zinc and CGP 35348 provide inhibition profiles which suggest that subtypes may exist. The identification of multiple subtypes of GABA$\sb{\rm B}$ receptors which are developmentally and/or regionally specific will lead to a more precise understanding of the role of GABA$\sb{\rm B}$ receptors in the development and function of the central nervous system. | |
dc.format.extent | 194 p. | |
dc.language | English | |
dc.language.iso | EN | |
dc.subject | Binding | |
dc.subject | Brain | |
dc.subject | Development | |
dc.subject | Distribution | |
dc.subject | Gaba$\sb{\rm B}$ | |
dc.subject | Pharmacology | |
dc.subject | Rat | |
dc.subject | Site | |
dc.title | Development of GABA(B) binding site distribution and pharmacology in rat brain. | |
dc.type | Thesis | |
dc.description.thesisdegreename | PhD | en_US |
dc.description.thesisdegreediscipline | Biological Sciences | |
dc.description.thesisdegreediscipline | Neurosciences | |
dc.description.thesisdegreegrantor | University of Michigan, Horace H. Rackham School of Graduate Studies | |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/129319/2/9423334.pdf | |
dc.owningcollname | Dissertations and Theses (Ph.D. and Master's) |
Files in this item
Remediation of Harmful Language
The University of Michigan Library aims to describe library materials in a way that respects the people and communities who create, use, and are represented in our collections. Report harmful or offensive language in catalog records, finding aids, or elsewhere in our collections anonymously through our metadata feedback form. More information at Remediation of Harmful Language.
Accessibility
If you are unable to use this file in its current format, please select the Contact Us link and we can modify it to make it more accessible to you.