Kinins are a family of peptides implicated in several pathophysiological events. Most of their effects are likely mediated by the activation of two G-protein-coupled receptors: B1 and B2. Whereas B2 receptors are constitutive entities, B1 receptors behave as key inducible molecules that may be upregulated under some special circumstances. In this context, several recent reports have investigated the importance of B1 receptor activation in certain disease models. Furthermore, research on B1 receptors in the last years has been mainly focused in determining the mechanisms and pathways involved in the process of induction. This was essentially favoured by the advances obtained in molecular biology studies, as well as in the design of selective and stable peptide and nonpeptide kinin B1 receptor antagonists. Likewise, development of kinin B1 receptor knockout mice greatly helped to extend the evidence about the relevance of B1 receptors during pathological states. In the present review, we attempted to remark the main advances achieved in the last 5 years about the participation of kinin B1 receptors in painful and inflammatory disorders. We have also aimed to point out some groups of chronic diseases, such as diabetes, arthritis, cancer or neuropathic pain, in which the strategic development of nonpeptidic oral-available and selective B1 receptor antagonists could have a potential relevant therapeutic interest.
British Journal of Pharmacology (2004) 143, 803–818. doi:10.1038/sj.bjp.0706012