This proposal concerns a widely distributed soluble angiotensin-binding protein that was originally discovered and purified. This protein probably mediates some of the actions of angiotensin II and the knowledge of its structure and regulation should be useful for understanding the mechanism of action of the octapeptide and for devising angiotensin antagonists as possible antihypertensive agents.
The specific aims of the proposal are: 1.To determine the primary structure of the soluble rabbit hepatic binding protein by cloning and sequencing the cDNA that encodes it. 2.To examine regulation of the similar soluble, immunologically homologous binding protein in cultured murine NlE-115 cells. These cells exhibit functional responses to angiotensin II and also contain well characterized angiotensin receptors on their membranes that are physiologically regulated. Emphasis will be on determining whether the regulation and/or structure of the soluble and membrane receptors is related; whether the functional effects of angiotensin II can be dissociated based on the properties of the two types of receptors; and whether the soluble protein can be physiologically recruited to and from membranes.
