KININ RECEPTORS & MECHANISMS OF ACTION
The biologic actions of kinins are mediated by specific receptors located on the membranes of the target tissues. Two types of kinin receptors, termed B1 and B2, have been defined based on the rank orders of agonist potencies; both are G protein-coupled receptors. (Note that B here stands for bradykinin, not for β adrenoceptor.) Bradykinin displays the highest affinity in most B2 receptor sys-tems, followed by lys-bradykinin and then by met-lys-bradykinin. One exception is the B2 receptor that mediates contraction of venous smooth muscle; this appears to be most sensitive to lys-bradykinin. Recent evidence suggests the existence of two B 2-receptor subtypes, which have been termed B2A and B2B.
B1 receptors appear to have a very limited distribution in mam-malian tissues and have few known functional roles. Studies with knockout mice that lack functional B1 receptors suggest that these receptors participate in the inflammatory response and may also be important in long-lasting kinin effects such as collagen synthe-sis and cell multiplication. By contrast, B2 receptors have a wide-spread distribution that is consistent with the multitude of biologic effects that are mediated by this receptor type. Agonist binding to B2 receptors sets in motion multiple signal transduc-tion events, including calcium mobilization, chloride transport, formation of nitric oxide, and activation of phospholipase C, phospholipase A2, and adenylyl cyclase.