Tissue kallikreins and kinins: regulation and roles in hypertensive and diabetic diseases.
The spectrum of cellular, or whole animal responses to kinins has expanded enormously in the last five years. The molecular basis for these consequences of kinin-kinin receptor interactions is being glimpsed as a series of cascading and parallel biochemical events occurring either in the same or adjacent, but communicating, cells of the same tissue (e.g. epithelial, endothelial, muscle, neural). Although it is likely that even more kinin-induced events remain to be discovered, like the interesting effects of the peptides on osteoclastic activity (128), a greater challenge in this field is the gathering of insights into precisely how the regulation of system component gene expression is coordinately carried out to allow component protein synthesis, transport and processing when necessary, and limitation of activities, when required. With these insights, we will be more able to understand the meaning of many observations of tissue kallikrein-kinin system abnormalities in common human diseases. This understanding will then make more obvious the drug design strategies to be used to stimulate or replace, and modulate or inhibit kallikrein-kinin system components in those diseases.
Margolius
H S
HS
Department of Pharmacology, Medical University of South Carolina, Charleston 29425.
D000818:Animals; D003920:Diabetes Mellitus / Q000503:physiopathology*; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D007610:Kallikreins / Q000378:metabolism* / Q000502:physiology; D007705:Kinins / Q000378:metabolism* / Q000502:physiology
D007705:Kinins; D007610:Kallikreins