Title: Experimental Approaches Using Kallikrein Gene Therapy for Hypertension
Abstract: The kallikrein gene family is a set of closely related serine proteinases that exhibit limited proteolysis of specific substrates [1–4]. All mammals studied have two types of kallikreins: plasma kallikrein and tissue kallikrein. They differ in primary structure, physico-chemical properties, immunological properties, substrate specificity, susceptibility to inhibitors, site of synthesis and biological function. Plasma kallikrein which is synthesized in the liver participates in blood coagulationand fibrinolysis in the circulation. Tissue kallikreins which are synthesized in various exocrine and endocrine organs, are involved in the processing of polypeptide hormones and growth factors [5]. Plasma kallikrein cleaves high molecular weight kininogen to produce bradykinin. Tissue kallikrein cleaves human and bovine low molecular weight kininogens to produce lysyl-bradykinin (kallidin) and in the rat it releases bradykinin from kininogen (Figure 1). Kinin binds to its receptorin target tissues and exhibits a broad spectrum of biological effects including: vasodilation, blood pressure reduction, smooth muscle relaxation and contraction, pain induction and inflammation [1,6]. There are two types of kinin receptors, B1 and B2 which differ in pharmacological properties, biological activities and primal) structures [6–11]. The B1 receptor binds weakly to intact kinin but strongly to kinin’s metabolites desArg9- bradykininand des-Arg10-kallidin, which are generated by kininase I. In contrast, the B2 receptor has a greater affinity to intact bradykinin and kallidin than to kinin’s metabolites [10]. The B1 receptor seems to be absent in normal mammalian tissues, but appears in pathological states such as inflammation and trauma while the B2 receptor is widely distributed throughout tissues [10,11].
Publication Year: 1997
Publication Date: 1997-01-01
Language: en
Type: book-chapter
Indexed In: ['crossref']
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