The Kallikrein‐Kinin System: Evolution of Form and Function^a

The Chemistry and Biological Activities of Peptides from Amphibian Skin Secretions

“…BRPs can be produced from circulating kininogens of typical species of different vertebrate taxa by trypsin treatment . However, amphibian plasma treated with enzymes generates an angiotensin-like peptide, not a BRP . Many studies have reported cDNA sequences encoding precursors of frog skin BRPs. ,− ,,,− These findings indicate that skin prepro-BK structures are not related to plasma kininogens; thus frog skin BRPs are not the products of enzyme catalysis by the kallikrein–kinin system.…”

“…Amphibians survive in various conditions with many predators and pathogens, and BK-like peptides in amphibian skin might have defensive functions alone or synergistically with other components. The diversity of BRPs in amphibian skin secretions reflects and might be dictated by their range of species-specific predators …”

Implications of Endothelial Cell-Mediated Dysfunctions in Vasomotor Tone Regulation

“…If, instead of Bradikinin binding to the B2 receptor of endothelial cells, it binds to the B2 receptor of SMC, it activates the Gq protein and subsequently directly activates PLC, leading to an increase in Ca 2+ concentration and to a constriction of vascular smooth muscle cells [141].…”

Ex Vivo Smooth Muscle Pharmacological Effects of a Novel Bradykinin-Related Peptide, and Its Analogue, from Chinese Large Odorous Frog, Odorrana livida Skin Secretions

“…It has subsequently been reported that, in mammals, endogenous BK is generated via the effect of kallikrein on kininogen, which was derived mostly from, but not restricted to, liver tissues [2,3]. Since the first amphibian canonical BK was reported in the defensive skin secretions systems in 1965 from Rana temporaria [4], numerous bradykinin-related peptides (BRPs), with extraordinary diverse primary structure flanked by C / N -terminal extension, were isolated and identified from the Ascaphidae, Hylidae, Ranidae and Bombinatatoridae families.…”

“…Of note is that mammals, reptiles, birds, and even fish were found to produce structurally discrete BRPs [5]. The research that focused on elucidating the hypervariable primary structures of BRPs across vertebrates was initially conducted by Conlon and his colleagues, and found that the diverse BRPs presented in unique vertebrate taxa all have identical counterparts in certain amphibian species [3,6]. Following on from this, the hypothesis was proposed that taxon-specific BRPs might be the most effective ligands for activating taxon-specific receptor mediated signal pathways, and for the improper BRP-ligands, they were believed to act as antagonists of the receptors to suppress the downstream signalling.…”