Degree Name

PhD (Doctor of Philosophy)

Program

Biomedical Sciences

Date of Award

May 1997

Abstract

The present studies explore binding, distribution, and function of angiotensin II (AII) receptors (AT$\sb1$ and AT$\sb2)$ in the brain. The discovery that sulfhydryl reducing agents masked some but not all AII receptors in the brain prompts an evaluation of commonly used binding assay buffer constituents. EDTA enhances binding (40%) at both AT$\sb1$ and AT$\sb2$ nuclei, while bacitracin did not alter binding at either receptor subtype. Phenanthroline and BSA differentially altered binding at AT1 (220% of control) and AT$\sb2$ (118% of control) receptors. The results indicate that phenanthroline and BSA would be poor buffer constituents for studies comparing binding at AT$\sb1$ and AT$\sb2$ receptors. All receptors were mapped in normotensive and genetically hypertensive hamster brains and the subtype composition estimated for a number of brain nuclei and the pituitary. Binding in the hamster was similar to that previously observed in the rat brain with exceptions: (1) additional binding in the medial habenula and interpeduncular nuclei, (2) absence of binding in the inferior olive, suprachiasmatic nucleus, medial amygdala, piriform cortex, and subthalamic nucleus and (3) quantitative differences in the dorsomotor nucleus of the vagus, striatum, hippocampus and anterior pituitary. Unlike studies of the normotensive and spontaneously hypertensive rat, we found no significant differences in binding distribution, density or subtype composition when comparing normal and genetically hypertensive hamsters. Finally, the effects of brain angiotensin II (AII) on central catecholamine utilization were determined. We found no significant differences in norepinephrine, epinephrine or dopamine utilization in rat brain homogenates following intracerebroventricular injection of AII. Although there is evidence that AII alters catecholamine utilization in some brain nuclei, these alterations appear limited (anatomically and/or quantitatively) to a relatively small portion of the brain catecholaminergic system. The results indicate that the selection of buffer constituents is an important consideration for AII binding studies, that there are minor species differences in the distribution of AII receptors in the brain and that despite substantial functional and anatomical overlap, only a relatively small portion of the brain catecholaminergic system is modulated by angiotensin II.

Document Type

Dissertation - Open Access

Included in

Neurology Commons

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