Kinin synthesis

The synthesis of kinins can be inhibited with the kallikrein inhibitor aprotinin. Actions of kinins mediated by prostaglandin generation can be blocked nonspecifically with inhibitors of prostaglandin synthesis such as aspirin. Conversely, the actions of kinins can be enhanced with ACE inhibitors, which block the degradation of the peptides. Indeed, as noted above, inhibition of bradykinin metabolism by ACE inhibitors contributes significantly to their antihypertensive action. 

It became clear, however, that in the whole plant the major site of cytokinin synthesis was in the roots from whence it was transported to the rest of the plant via the xylem transpiration stream. Perhaps kinins were a kind of rhizocaline ... 

Bi receptors may also be important in long-lasting kinin effects such as collagen synthesis and cell multiplication. By contrast, B2 receptors have a widespread distribution that is consistent with the multitude of biologic effects that are mediated by this receptor type. B2 receptors belong to the G protein-coupled family of receptors. Receptor binding sets in motion multiple signal transduction... 

Bradykinin and related kinin peptides are produced by leucocytes and act via Gaq to elevate cytosolic Ca2+ and promote nitric oxide (NO) synthesis, smooth muscle contraction, capillary permeability, inflammation and histamine release from mast cells. 

In fact, a medley of substances (autacoids), kinins, prostaglandins, leukotrienes, histamine, endorphins, serotonin, vasopressin, has been implicated. In endotoxic shock, the toxin also induces synthesis of nitric oxide, the endogenous vasodilator, in several types of cells other than the endothelial cells which are normally its main source. 

Sulfinpyrazone, a uricosuric congener of phenylbutazone, also causes hemodynamically-mediated acute renal failure. Sulfinpyrazone inhibition of renal prostaglandin synthesis or reduction of renal kallikrein-kinin activity may imbalance renal hemodynamics, causing renal ischemia. Renal insufficiency may be transient despite continued sulfinpyrazone administration or prolonged and oliguric with a low urinary sodium concentration. 

Zabrocki, J., Dunbar, J. B. Jr., Marshall, K. W., Toth, M. V., and Marshall, G. R. (1992) Conformational mimicry. Part III. Synthesis and incorporation of 1,5-disubstituted tetrazole dipeptide analogs into peptides with preservation of chiral integrity Brady-kinin./. Org. Cbem. 57, 202-209. 

A vasodilating peptide with smooth-muscle stimulating action was described by Rocha e Silva, Beraldo and Rosenfeld in 1949 and named bradykinin. It is produced by the action of trypsin or snake venoms on plasma. A similar substance, kallidin, was prepared shortly afterwards by Werle and Berek using the protease kalUkrein. Other peptides with similar properties have been described and the general term kinins or, when derived from plasma proteins, plasma kinins has been recommended. The best-known kinin, bradykinin, has recently been shown to be a nonapeptide, and its structure confirmed by synthesis - . When injected subcutaneously into laboratory animals and man, bradykinin causes vasodilatation, increased vascular permeability, leucocyte infiltration and pain. 

In addition, the kidneys have direct endocrine functions. Because they are a major site of synthesis of several hormones, including erythropoietin and 1,25-dihydroxy-cholecalciferol, the kidneys indirectly influence the regulation of blood pressure and vasopressor activity via the renin-angiotensin, prostaglandins, and kallekrein-kinin systems, which exert a regulatory effect on water and electrolyte homeostasis (Harris 1992 Parekh et al. 1993 Gonzalez et al. 1998 Campean et al. 2003 see also Chapters 6 and 10). 

The Endogenous Kallikrein-Kininogen-Kinin System SYNTHESIS AND METABOLISM OF KININS... 

Grenier, F.C., Rollins, T.E. and Smith W.L. (1981). Kinin-induced prostaglandin synthesis by renal papillary collecting tubule cells in culture. Am. ]. Physiol, 241, F94-F104... 

E. Schroder, Peptide Syntheses. Synthesis of Methionyllysylhradykinin, a Kinin from Bovine Blood, Experientia 20, 39 (1964). 

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