PT  - JOURNAL ARTICLE
AU  - Leeb-Lundberg, L. M. Fredrik
AU  - Marceau, Francois
AU  - Müller-Esterl, Werner
AU  - Pettibone, Douglas J.
AU  - Zuraw, Bruce L.
TI  - International Union of Pharmacology. XLV. Classification of the Kinin Receptor Family: from Molecular Mechanisms to Pathophysiological Consequences
AID  - 10.1124/pr.57.1.2
DP  - 2005 Mar 01
TA  - Pharmacological Reviews
PG  - 27--77
VI  - 57
IP  - 1
4099  - http://pharmrev.aspetjournals.org/content/57/1/27.short
4100  - http://pharmrev.aspetjournals.org/content/57/1/27.full
SO  - Pharmacol Rev2005 Mar 01; 57
AB  - Kinins are proinflammatory peptides that mediate numerous vascular and pain responses to tissue injury. Two pharmacologically distinct kinin receptor subtypes have been identified and characterized for these peptides, which are named B1 and B2 and belong to the rhodopsin family of G protein-coupled receptors. The B2 receptor mediates the action of bradykinin (BK) and lysyl-bradykinin (Lys-BK), the first set of bioactive kinins formed in response to injury from kininogen precursors through the actions of plasma and tissue kallikreins, whereas the B1 receptor mediates the action of des-Arg9-BK and Lys-des-Arg9-BK, the second set of bioactive kinins formed through the actions of carboxypeptidases on BK and Lys-BK, respectively. The B2 receptor is ubiquitous and constitutively expressed, whereas the B1 receptor is expressed at a very low level in healthy tissues but induced following injury by various proinflammatory cytokines such as interleukin-1β. Both receptors act through Gαq to stimulate phospholipase Cβ followed by phosphoinositide hydrolysis and intracellular free Ca2+ mobilization and through Gαi to inhibit adenylate cyclase and stimulate the mitogen-activated protein kinase pathways. The use of mice lacking each receptor gene and various specific peptidic and nonpeptidic antagonists have implicated both B1 and B2 receptors as potential therapeutic targets in several pathophysiological events related to inflammation such as pain, sepsis, allergic asthma, rhinitis, and edema, as well as diabetes and cancer. This review is a comprehensive presentation of our current understanding of these receptors in terms of molecular and cell biology, physiology, pharmacology, and involvement in human disease and drug development.