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Tiir COUNCIL Fciz Teuncco RL~LaRCU-U.S.A., IIYc. September 3, 1974 MEMORANDUM TO: Drs. Bing, Hockett, Liebow, Nordsiek and Sommers FROM: W. U. Gardner I i i:4 l `-. t',)41 1.'s SUBJECT: Application 814-A. Una Smith Ryan, Ph.D., Cardiopulmonary Unit, Papanicolaou Cancer Research Institute, Miami, Florida. "Endocrine Functions of the Lungs." This proposal continues to be described as a study on angiotensin and the localization of angiotensin degrading enzyme. This is a continuation of earlier work. The unique aspect of the problem is that the lurlg endothelium converts the ten peptide angiotensin I to the eight peptid,e angiotensin II with one passage of the blood. Renim is presumably the rate-limiting step in the process as it forms angiotensin I from a liver-produced alpha glo}iulin. The regulation of renin release is the prime factor. The lung also produces an enzyme that destroys bradykinin as well as adenine nucleotides (hydrolyses). They have a goat antibody to hog angiotensin I and have developed methods for testing and purifying it. Microperoxidase (molecular weight 2000) has been coupled to the antibody by glutaryladehyde. Methods of preserving the tissues and getting localization of the antibomicroperoxidase have been worked out. Much of the luminal endothelial wall localizes it but especially the caveolea. They are going to attempt othe r antibody binding markers and outline plans that may be followed. They plan further studies on the bradykinin- destroying enzyme which seems quite nonspecif ic. It seem to me that the problem of angiotensinIase localization is rather running out and that its significance declines because it seems not to be a rate- limiting factor in the renin-angiotensin scheme. Mention is made of the availability of nicotine and cotenine-BSA conjugates and the possibility of binding them to suitable,e.m. markers. The nicotine marker,should be available in January, the cotenine one in the spring. I think that a one-year extension is indicated. W.U.G. WUG:ek