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Bradykinins, analogs, and sequences are a class of a physiological and pharmacologically active peptide containing nine amino acids derived from the kinin group of the protein. The structural order of bradykinin is Arg, Pro, Pro, Gly, Phe, Ser, Pro, Phe, Arg. They are mainly present in tissues and contain less blood, which is formed by high molecular weight kininogens under the action of plasma kallikrein and acts in a paracrine and autocrine manner. They are effectors that promote vasodilation, increased vascular permeability, nitric oxide release, and arachidonic acid flow. They act as important regulators of blood pressure, kidney function, and heart function, and are also involved in the inflammatory response. Bradykinins, analogs, and sequences cause blood vessels to dilate, resulting in a decrease in blood pressure. RMP-7 is a synthetic bradykinin analog. RMP-7 contains three unnatural amino acid substitutions at positions 3, 5, and 8 of bradykinin, and a reducing peptide bond between positions 8 and 9. Because of the specificity of this structure, RMP-7 has higher bradykinin receptor selectivity and longer plasma half-life than bradykinin.
The physiological role of bradykinin is mediated by its receptor. The bradykinin receptor is divided into two subtypes, B1 and B2, which are G-protein coupled receptors. The B1 receptor is characterized by low affinity and is not easily saturated. The B1 receptor may be involved in the pathological process of slow pain and inflammation. The B2 receptor is present in many tissues and it mediates most of the response of bradykinin. The B2 receptor has a high affinity, and the bradykinin has the highest affinity for the B2 receptor in the agonist. When bradykinin binds to the B2 receptor, it triggers a series of signaling reactions, including Ca2+ influx, G protein activation, and a series of kinase activation processes.
At present, the use of bradykinin or its analog, such as RMP-7, to selectively open the blood-brain barrier is one of the most effective adjuvant treatments. In countries such as Europe and the United States, the use of bradykinin or its analog RMP-7 to treat brain tumors has entered the stage of clinical trials. Their application is expected to make breakthroughs in the treatment of brain diseases.
Reference
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