| Research Abstract |
Studies on vasoactive peptides and their related proteolytic enzymes are important for understanding the regulatory mechanisms underlying blood pressure control and the pathogenesis of essential hypertension. This research project concerns the investigations on the molecular and genetic aspects of the renin-angiotensin, kallikrein-kinin, tachykinin and atrial natriuretic factor (ANF) systems.
Under this project, we have succeeded in isolating and characterizing cDNAs and genomic DNAs for renin, angiotensinogen, kallikrein, kininogen, ANF precursor and preprotachykinins A and B. These studies have led to a detailed comprehension of the structures, gene organizations and regulations of the peptide precursors and their related enzymes. The elucidation of the structures of the peptide precursors have revealed that they not only serve as precursors for vasoactive peptides but also bear multifunctional properties associated with other biological systems (e.g. structural similarity of angiotensinogen with other serine protease inhibitors, identity of kininogen and cysteine proteinase inhibitor, a common precursor for ANF and cardiodilatin, and existence of an additional tachykinin within preprotachykinin A). Detailed studies on the gene expressions have indicated that each of the genes is regulated quantitatively and qualitatively by effectively utilizing various cellular mechanisms characteristic of higher eukaryotic cells (e.g. differential expression of the kininogen genes and the preprotachykinin A and B genes, alternative RNA processing of the kininogen gene and the preprotachykinin A gene, and tissue-specific expressions of the renin, kallikrein and ANF precursor genes). Thus, the studies conducted under this research project have unraveled fundamental molecular mechanisms underlying the regulation of the above biological systems and have provided many important clues for further investigations on blood pressure control and pathogenesis of essential hypertension.
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