Adrenal steroid regulation of central angiotensin II receptor subtypes in brain / Suresh Girish Shelat.

Format:

Book

Manuscript

Microformat

Thesis/Dissertation

Author/Creator:

Shelat, Suresh Girish.

Contributor:

Fluharty, Steven J., advisor.

Nusbaum, Mike, advisor.

University of Pennsylvania.

Language:

English

Subjects (All):

Penn dissertations--Neuroscience.

Neuroscience--Penn dissertations.

Neurosciences.

Academic Dissertations as Topic.

Medical Subjects:

Neurosciences.

Academic Dissertations as Topic.

Local Subjects:

Penn dissertations--Neuroscience.

Neuroscience--Penn dissertations.

Physical Description:

viii, 120 pages : illustrations ; 29 cm

Production:

1998.

Summary:

Mineralocorticoids and angiotensin II (AngII) are two of the principal hormones of sodium homeostasis. While these hormones act in the periphery to conserve sodium, they act synergistically in the brain to elicit a sodium appetite. However, it is unclear which nuclei may mediate mineralocorticoid regulation of AngII receptors. Thus, receptor autoradiography was used to quantify the changes in AngII receptor type-1 (AT1) and type 2 (AT2) receptor subtypes in specific nuclei of the rat forebrain and brainstem following changes in adrenal steroids. Adrenalectomy (ADX) resulted in decreased AT1 receptor binding in the hypothalamic paraventricular nucleus of the hypothalamus (PVN), subfornical organ (SFO), and the area postrema. However, there were no changes in AT2 receptor binding. Similarly no changes in oxytocin receptor binding were detected, indicating that the central inhibitory actions of oxytocin on salt appetite were not apparent at the level of the oxytocin receptor.

The SFO, PVN, and area postrema were responsive to changes in adrenal steroids, whether they were depleted after ADX or elevated following exogenous administration. During sodium depletion, there are elevations in both mineralocorticoid and AngII that act synergistically in the brain to elicit salt appetite. In addition, glucocorticoids may enhance the effects of AngII and mineralocorticoids. However, the nuclei that mediate this behavioral synergy are not known. This study suggests that mineralocorticoids and glucocorticoids act together at the SFO and area postrema to increase salt appetite and sensitize the brain to the actions of AngII.

Since the in vivo results may have reflected indirect actions of steroids on AT1 receptor levels, in vitro experiments examined the direct actions of adrenal steroids. Activation of the glucorticoid receptor increased AT1 receptor binding and also increased AngII-induced inositol 1,4,5 trisphosphate formation. The results of this study suggest that the tonic activation of mineralocorticoid receptor to maintain basal AT1 receptors in vivo and the behavioral synergy between mineralocorticoid, glucocorticoids, and AngII may involve multiple nuclei involved in salt appetite, including the SFO, PVN, and area postrema.

Notes:

Advisers: Steven J. Fluharty; Mike Nusbaum.

Thesis (Ph.D. in Neuroscience) -- University of Pennsylvania, 1998.

Includes bibliographical references.

Local Notes:

University Microfilms order no.: 98-29988.

OCLC:

187470859