Our overall aim is to determine what specific cell types bind angiotensin II (AII) in order to better understand its known effects on the secretion of a variety of hormones. For example, in the hypothalmopituitary system, which has AII receptors at both ends of the portal plexus we want to know whether the peptide is acting at the level of the releasing factor neuron, the pituitary, or a combination of the two.
The specific aims of this proposal are: (1) To evaluate the time course and binding of mono-I-125-AII by the rat hypothalmus, pituitary, and adrenal. The goal will be to identify the specific cell types which bind, and possibly internalize labeled AII. This goal will be accomplished by counting bound radioactivity, by evaluating the nature of the label, and by performing parallel autoradiographic analysis of the distribution of the label in relation to specifically immunocytochemically identified cells at the light microscopic level. (2) Using the results of #1 as a guide, the distribution of bound labeled AII will be studied at the ultrastructural level using simultaneous autoradiography and immunocytochemistry. Immunocytochemistry will be directed at the cells in question primary secretory product and AII (in cells demonstrated to contain AII at the light level). (3) The role of the brain and renal renin-angiotensin (RAS) system in events occurring at the level of the median eminene will be studied in experimentally manipulated rats. These studies will employ normal, adrenalectomized, rats with unilateral renal hypertension. This work is of fundamental importance in understanding specific AII sites of action which stimulate the release of a variety of hormones important in cardiovascular, metabolic, and reproductive processes.
