Kinin Receptors and Their Antagonists as Novel Therapeutic Agents

Abstract

Plasma kinins are a family of peptides which play an important role in a variety of pathophysiological conditions. As a consequence of the progress in the area of kinin receptors, specific kinin receptor antagonists will be available in near future in order to provide more selective therapeutic modalities for the treatment of diseases such as asthma, cardiovascular diseases, inflammation, pain, etc. Although the initial observation leading to discovery of kinins has been performed in 1909, important progress on the development of specific kinin receptor antagonists has been made in last two decades. This review emphasizes the physiological functions of kinins along with their receptor subtypes and post-receptor events in the cellular signaling. In this article, the latest developments in the kinin receptor antagonists including nonpeptide ones have been reviewed.

Peptide IC-20, encoded by skin kininogen-1 of the European yellow-bellied toad, Bombina variegata, antagonizes bradykinin-induced arterial smooth muscle relaxation

“…[3–78–1112–13] What has become clear is that such amphibian secretions represent a unique resource for the discovery of natural structural variants of the canonical mammalian peptide and that many of these are homologs of forms found in submammalian vertebrates. [910] The wide range of variants is thought to be due to molecular tailoring of core structures through natural selection to provide the most effective spectrum of agents to deter predation by specific predator groups.…”

“…Bradykinin inhibitors are clearly applicable as possible treatment options for pathological processes such as chronic pain and chronic inflammatory disorders, such as rheumatoid arthritis and inflammatory bowel disease. [1218] Allergic asthma has also been linked to an exaggerated and persistent response to bradykinin resulting in bronchospasm. [19] Through its autocrine growth factor function, bradykinin has also been linked as a causative agent in tumor growth and metastasis, by facilitating angiogenesis and promoting the VEGF and MMP activity.…”

“…[19] Through its autocrine growth factor function, bradykinin has also been linked as a causative agent in tumor growth and metastasis, by facilitating angiogenesis and promoting the VEGF and MMP activity. [1218] Thus, the discovery of naturally occuring bradykinin inhibitors with unique structures that may act through novel mechanisms in the blocking of bradykinin signaling could provide the medicinal chemist with a range of potential lead compounds for future drug development programs or could shed new light on the pharmacological mechanisms of bradykinin action.…”