Kallikreins and kininogenases (kinin-generating enzymes) are serine proteases with limited and specific proteolytic capability. The existence of a large kallikrein gene family (announced at the last Gordon Conference); the diversity of localization sites including: plasma, sperm, peripheral exocrine glands and their secretions, renal and intestinal epithelial cells, various brain nucleii, pituitary and pineal, red blood cell membrane and other formed elements of blood, the vascular wall, as well as closely related enzymes in invertebrates and bacteria; the possibility that the """"""""kallikrein-kinin"""""""" system is but a paradigm for many other kallikrein-regulated, substrate-product systems because tissue kallikreins can attack several newly identified substrates, (e.g., atrial natriuretic factor precursors, apolipoprotein B100); are all reasons for a markedly heightened interest since the 1983 Gordon Conference. It is now being suggested that the tissue kallikrein gene family may be responsible for the synthesis of several closely-related kallikreins with diverse, but bond-specific proteolytic activities which regulate the elaboration of many peptide hormones. This exciting idea is being tempered by the realization that there is, as yet, no proof that tissue kallikreins act upon any endogenous substrates, other than kininogens. Data are being gathered in many laboratories which addresses this issue, most important to the full description of the functional responsibilities of the kallikreins and of the kinins. A family of long-awaited and newly synthesized kinin antagonists are beginning to be used in these tasks. In addition, other recent advances in the study of kallikreins and kinins have been made using state-of-the-art technologies in molecular genetics and biology, biophysics, synthetic and organo-analytical chemistry, and immunology. Thus, the study of kallikreins and kinins has reached a most exciting point with health-related implications to cardiovascular, metabolic, endocrinologic, inflammatory and malignant diseases. The purpose of this proposal is to request funds to further facilitate these studies by partially supporting the third Gordon Research Conference on Kallikreins and Kinins. This conference, as its predecessors, will serve to further stimulate both new and established investigators to new discovery in this area of endeavor.
