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A study of the localization and traf...
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Garcia Cazarin, Mary Lolis.
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A study of the localization and trafficking properties of the alpha1D-adrenoceptor using adenoviral vectors in human aortic smooth muscle cells.
紀錄類型:
書目-語言資料,印刷品 : Monograph/item
正題名/作者:
A study of the localization and trafficking properties of the alpha1D-adrenoceptor using adenoviral vectors in human aortic smooth muscle cells./
作者:
Garcia Cazarin, Mary Lolis.
面頁冊數:
127 p.
附註:
Advisers: Michael T. Piascik; Susan D. Kraner.
Contained By:
Dissertation Abstracts International67-09B.
標題:
Health Sciences, Pharmacology. -
電子資源:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3231187
ISBN:
9780542848070
A study of the localization and trafficking properties of the alpha1D-adrenoceptor using adenoviral vectors in human aortic smooth muscle cells.
Garcia Cazarin, Mary Lolis.
A study of the localization and trafficking properties of the alpha1D-adrenoceptor using adenoviral vectors in human aortic smooth muscle cells.
- 127 p.
Advisers: Michael T. Piascik; Susan D. Kraner.
Thesis (Ph.D.)--University of Kentucky, 2006.
The alpha1-adrenoceptors (alpha1-ARs) belong to the G-protein coupled receptor (GPCR) superfamily. They play an integral role in the regulation of blood pressure, ionotropy, and growth responses. Three alpha1-ARs have been cloned and characterized: alpha 1A-AR, alpha1B-AR and alpha1D-AR.
ISBN: 9780542848070Subjects--Topical Terms:
1017717
Health Sciences, Pharmacology.
A study of the localization and trafficking properties of the alpha1D-adrenoceptor using adenoviral vectors in human aortic smooth muscle cells.
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127 p.
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Advisers: Michael T. Piascik; Susan D. Kraner.
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Source: Dissertation Abstracts International, Volume: 67-09, Section: B, page: 5003.
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The alpha1-adrenoceptors (alpha1-ARs) belong to the G-protein coupled receptor (GPCR) superfamily. They play an integral role in the regulation of blood pressure, ionotropy, and growth responses. Three alpha1-ARs have been cloned and characterized: alpha 1A-AR, alpha1B-AR and alpha1D-AR.
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This dissertation project is the natural extension of findings by previous students in this laboratory and is designed to increase our understanding of the localization and regulatory function of the alpha1-ARs. Based on trafficking properties, the alpha1B-AR is considered a prototype GPCR; it localizes in the cell surface and undergoes agonist-mediated desensitization and internalization. In contrast, the alpha1D-AR is an atypical GPCR; it localizes mainly inside the cell and does not undergo agonist-mediated desensitization or internalization.
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To facilitate the study of the localization and trafficking properties of the alpha1D-AR, we developed adenoviral vectors for the efficient expression of the alpha1B-AR and the alpha1D-AR in fibroblasts stably transfected with the alpha1-ARs and vascular smooth muscle cells. In addition, physiological studies, calcium transient measurements in cells, and contractile studies in transgenic mice and rats were incorporated to further investigate the role of the alpha1-ARs in complex systems.
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A major finding of this dissertation project is that in human aortic smooth muscle cells a significant degree of surface expression and agonist-mediated internalization was noted for the alpha1D-AR. These data suggest that the presence of other alpha1-AR subtypes in smooth muscle cells alters alpha1D-AR localization. In addition, our data support the idea that the alpha1D-AR can dimerize with either the alpha 1A-AR or alpha1B-AR. Results from calcium transient measurements demonstrated that the alpha1D-AR is coupled to increases of intracellular calcium. Moreover, contractile responses in rat and transgenic mouse blood vessels did not detect evidence that interaction with other adrenoceptors alters the characteristics of the alpha1D-AR.
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In summary, these data increase our understanding of the localization, trafficking, and, regulatory activities of the alpha1-ARs with emphasis on the alpha1D-AR. This information not only increases our understanding of the basic regulatory activities of the alpha1 -ARs, but also of potential sites where interference with these activities may result in cardiovascular pathophysiology.
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