MOLECULAR-BIOLOGY OF THE KALLIKREIN-KININ SYSTEM - FROM STRUCTURE TO FUNCTION

The participation of the kallikrein-kinin system, comprising the serin e proteases kallikreins, the protein substrates kininogens and the eff ective peptides kinins, in some pathological processes like hypertensi on and cardiovascular diseases is still a matter of controversy. The u se of different experimental set-ups in concert with the development o f potent and specific inhibitors and antagonists for the system has hi ghlighted. its importance but the results still lack conclusivity. Ove r the last few years, transgenic and gene-targeting technologies assoc iated with molecular biology tools have provided specific information about the elusive role of the kallikrein-kinin system in the control o f blood pressure and electrolyte homeostasis. cDNA and genomic sequenc es for kinin receptors B2 and B1 from different species were isolated and shown to encode G-protein-coupled receptors and the structure and pharmacology of the receptors were characterized. Transgenic animals e xpressing an overactive kallikrein-kinin system were established to st udy the cardiovascular effects of these alterations and the results of these investigations further corroborate the importance of this syste m in the maintenance of normal blood pressure. Knockout animals for B2 and B1 receptors are available and their analysis also points to the role of these receptors in cardiovascular regulation and inflammatory processes. In this paper the most recent and relevant genetic animal m odels developed for the study of the kallikrein-kinin system are revie wed, and the advances they brought to the understanding of the biologi cal role of this system are discussed.