Kinin Receptors & Mechanisms of Action

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 B_2A and B_2B.

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.