Hypotensive peptides bradykinin

An important discovery in the field of peptide synthesis was made by R. Bruce Merrifield (United States 1921-2006) in 1962. He was able to bind an amino acid to a polymer bead via the C-terminus and subsequently synthesized the peptide bradykinin (arg-pro-pro-gly-phe-ser-pro-phe-arg a potent hypotensive agent) by doing the chemical reactions, including the protection and deprotection steps, on a polymer bead. When completed, the nonapeptide was released from the polymer by a simple chemical reaction. This basic approach is now called the Merrifield synthesis and is one of the most important advancements in peptide synthesis. 

Kinins have been classified as hypotensive peptides resembling bradykinin in both structure and pharmacologic activity (1). 

When injected intravenously, kinins produce a rapid fall in blood pressure that is due to their arteriolar vasodilator action. The hypotensive response to bradykinin is of very brief duration. Intravenous infusions of the peptide fail to produce a sustained decrease in blood pressure prolonged hypotension can only be produced by progressively increasing the rate of infusion. The rapid reversibility of the hypotensive response to kinins is due primarily to reflex increases in heart rate, myocardial contractility, and cardiac output. In some species, bradykinin produces a biphasic change in blood pressure—an initial hypotensive response followed by an increase above the preinjection level. The increase in blood pressure may be due to a reflex activation of the sympathetic nervous system, but under some conditions, bradykinin can directly release catecholamines from the adrenal medulla and stimulate sympathetic ganglia. Bradykinin also increases blood pressure when injected into the central nervous system, but the physiologic significance of this effect is not clear, since it is unlikely that kinins cross the blood-brain barrier. 

Bradykinin and kallidin ate potent vasodilators and hypotensive agents that have different peptide structures bradykinin is a nonapeptide, whereas kallidin is a decapepttde. Kdlidin is ly.syl-bradykinin that is. it has an additional lysine at the NH2 terminus of the chain. Tliese two compounds arc made available from kininogen. a hlood globulin, on hydrolysis. Trypsin, plasmin, or the proteases of certain snake venoms can catalyze the hydrolysis of kininogen. 

Thi ,DPhe BK [Thi ,DPhe ]-bradykinin. bradykinin-potentiating peptide teprotide. bradykinin potentiator B teprotide. BRADYKININ RECEPTOR AGONISTS act at sites recognizing members and derivatives of the bradykinin family of hormone peptides - kinins - of which bradykinin (BK) and kallidin (lysyl-bradykinin Lys-BK KD) are the main mammalian members. The bradykinin family is distinct from the tachykinin family of peptides, though both have profound hypotensive actions and contract many intestinal and other smooth muscles. Historically, it was noted that the former action was relatively slow-developing, hence the name bradykinin. Notable actions of bradykinin and kallidin are to dilate blood vessels and increase their permeability to plasma proteins, and to stimulate sensory nerve C-fibres. These actions are pro-inflammatory, and reflect the fact that the kinin-formation system is activated in inflammation, and enzymes (kallikreins) form the kinins from blood-borne or tissue precursors (kininogens) on injurious insult. 

The vasodilating action of caerulein and I.C.I. 50,123 on the pancreaticoduodenal vessels seems to be peculiar to these peptides only eledoisin, a peripheral vasodilating peptide, but not brady-kinin increased temporarily for 15-30 seconds the pancreaticoduode nal blood flow. This effect was followed promptly by a decrease in flow when blood pressure dropped. Similarly the hypotension caused by bradykinin was accompained by a corresponding decrease in blood flow. 

---