Bradykinin pathway

Fig. 28.3. Schematic representation of the bradykinin pathway and its relationship to ACE and the renin-angiotensin pathway.

Cl inhibitor deficiency causes angioedema as a result of excessive bradykinin production. Thus the pathways and control mechanisms for bradykinin formation and... 

DKPs are simple and easy to obtain and are quite common by-products of synthetic, spontaneous, and biological formation pathways. DKP formation has been well documented as side reactions of solid-phase and solution-phase peptide synthesis. In addition, DKPs have been shown to be decomposition products of various peptides, proteins, and other commercial pharmaceuticals. Cyclic dipeptides were found to be present in solutions of human growth hormone, bradykinin, histerlin, and solutions of agents within the classes of penicillins and cephalosporins. " DKPs are also enzymatically synthesized in several protists and in members of the plant kingdom. Hydrolysates of proteins and polypeptides often contain these compounds and they are commonly isolated from yeasts, lichens, and fungi. ... 

The kallikrein-kinin system is an enzymatic pathway giving rise to two predominant vasoactive peptides, kallidin and bradykinin. Kallikrein, the enzyme responsible for the formation of these peptides, exists in plasma and tissues. However, circulating levels of the end products, kalhdin and bradykinin, are quite low because the kalhkrein enzymes are present largely in inactive forms. In addition, the short half-life of these peptides (15 seconds) also contributes to low plasma levels. In general, the kinins produce relaxation of vascular smooth muscle and vasodilation. Bradykinin causes... 

The AT2 receptor has a structure and affinity for Ang II similar to those of the A receptor. In contrast, however, stimulation of AT2 receptors causes vasodilation that may serve to counteract the vasoconstriction resulting from ATi receptor stimulation. AT2 receptor-mediated vasodilation appears to be nitric oxide (NO)-dependent and may involve the bradykinin B2 receptor-NO-cGMP pathway. 

The pathway for the formation and metabolism of kinins is shown in Figure 17-4. Three kinins have been identified in mammals bradykinin, lysylbradykinin (also known as kallidin), and methionyllysylbradykinin. Each contains bradykinin in its structure. 

The bradykinin receptor is a member of a family of receptors for which an intracellular interaction with a G-protein is a critical part of the signal transduction pathway following agonist binding. Structurally, these G-protein-coupled receptors extend from beyond the extracellular boundary of the cell membrane into the cytoplasm. The tertiary structure is such that the protein crosses the bilayer of the cell membrane seven times, thus forming three intracellular loops, three extracellular loops, and giving rise to cytoplasmic C-terminal and extra-cellular N-terminal strands. It is generally presumed that the transmembrane domains of these receptors exist as a bundle of helical strands. This assumption is derived primarily from the known structure of the trans-membrane portions of a structurally related protein, bacteriorhodopsin [40]. 

Sanovich, E., et al. 1995. Pathway across blood-brain barrier opened by the bradykinin agonist, RMP-7. Brain Res 705 125. 

Scholze T, Moskvina E, Mayer M et al (2002) Sympathoexcitation by bradykinin involves Ca2+-independent protein kinase C. J Neurosci 22 5823-32 Schwartz EJ, Blackmer T, Gerachshenko T et al (2007) Presynaptic G-protein-coupled receptors regulate synaptic cleft glutamate via transient vesicle fusion. J Neurosci 27 5857-68 Searl TJ, Silinsky EM (1998) Increases in acetylcholine release produced by phorbol esters are not mediated by protein kinase C at motor nerve endings. J Pharmacol Exp Ther 285 247-51 Seino S, Shibasaki T (2005) PKA-dependent and PKA-independent pathways for cAMP-regulated exocytosis. Physiol Rev 85 1303 12... 

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