We propose to characterize the different forms of angiotensinogen mRNA in the rat, measure the relative accumulation of these mRNAs in various tissues and determine whether the various angiotensinogens encoded by these mRNAs are capable of acting as renin substrates. Angiotensinogen is a 55,000-60,000 dalton serum glycoprotein, whose only known function is to act as a precursor to the decapeptide, angiotensin I, which is in turn rapidly converted to the octapeptide hormone, angiotensin II. Ang II is a potent vasopressor and regulates mineral balance, primarily through regulation of mineral corticoid synthesis. We have recently discovered multiple forms of angiotensinogen mRNA in the rat and will characterize these mRNAs by determining the nucleotide sequence of the corresponding cDNAs. This sequence information will be used to develop hybridization probes specific for each form of angiotensinogen mRNA. To determine whether the angiotensinogens encoded by the mRNAs have the potential to be renin substrates we will synthesize each angiotensinogen mRNA in vitro, translate these mRNAs in vitro or, if necessary, in ovo, and test the secreted angiotensinogen for susceptibility to proteolysis by renin. This research has the potential of describing new roles for angiotensinogen as a precursor to other peptide hormones.
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