Bradykinin

Bradykinin (H-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg-OH) releases bronchodilator NO from the airway epithelium (Ricciardolo et al. 2000). Bradykinin-induced NO release was higher in tracheal than in main bronchial segments of the guinea pig. The selective bradykinin Bj receptor antagonist D-Arg°- [Hyp Thi D-Tic, Oic ]bradykinin (1 jiM) inhibited NO release induced by a submaximum concentration of bradykinin (1 juM). 

In screening studies against the guinea pig bradykinin B2 receptor, Sal-vino et at Sterling Winthrop Pharmaceuticals discovered a bis phos- 

Kyle et al.i - have used the program CHARMm to perform extensive conformational analyses in the investigation of possible P-turn mimetics for incorporation into the C-terminal region of bradykinin and its derivatives. 

They used the conformational maps of mimetics to determine the geometry of recognition cavities on the BK receptor, 

As discussed in Section 3.3, few histopathological studies of asthma have focused specifically on the microvasculature. Nonetheless, there is evidence that neovascularization is one of the changes in the airways of asthmatics (Kuwano et al., 1991). This observation in potentially important because newly formed blood vessels may be abnormally leaky (Schoefl, 1967) or abnormally responsive to inflammatory mediators (McDonald, 1992). The plasma leakage that occurs in the airway mucosa of asthmatics could result from the heightened response of the mucosal blood vessels to inflammatory mediators. 

Several mechanisms app ear to be involved in the potentiation of neurogenic plasma leakage by M. pulmonis infection. There is an increase in the number of mucosal 

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Numerous neuropeptides are beheved to be involved with the transmission or inhibition of pain, and the hope is to utilize this approach as a strategy to induce analgesia. Substance P is reported to be a transmitter of nociceptive impulses (39), and therefore antagonists should be analgesic. Capsaicin [404-86-4], C2gH2yN02, is known to deplete substance P and cause analgesia (40), but its side effects are intolerable. Antagonists to bradykinin [58-82-2], a substance known to induce pain (41), have shown some success in preclinical trials. 

Two different mixtures of peptides and alkaloids (qv) have been analy2ed by ce/uv/ms using sims to determine whether this technique can detect trace impurities in mixtures (85). The first mixture consisted of two bioactive peptide analogues, which included Lys-bradykinin (kahidin) and Met-Lys-bradykinin. The presence of 0.1% Lys-bradykinin was detected by sim ce/ms but not by ce/uv at 0.1% level as it migrated from the capillary column prior to the main component, Met-Lys-bradykinin. The second mixture consisted of two antibacterial alkaloids, berberine and palmitine. The presence of 0.15% palmitine was detected by ce/uv and sim ce/ms at 0.15% level as it migrated from the capillary column, following the main component berberine. This technique can provide a complementary technique for trace components in such sample mixtures. 

Other mechanisms of action, such as potentiation of the bradykinin [58-82-2] effect, and increased production of prostaglandins... 

A reevaluation of the original sequence data established that natural bradykinin was indeed the nonapeptide shown. Here the synthesis of a peptide did more than confirm str-ucture synthesis was instrumental in determining structure. 

By successively adding anino acid residues to the C-terminal amino acid, it took Menifield only eight days to synthesize bradykinin in 68% yield. The biological activity of synthetic bradykinin was identical with that of natural material. 

How many peaks would you expect to see on the strip chart after amino acid analysis of bradykinin ... 

The release of arachidonate and the synthesis or interconversion of eicosanoids can be initiated by a variety of stimuli, including histamine, hormones such as epinephrine and bradykinin, proteases such as thrombin, and even serum albumin. An important mechanism of arachidonate release and eicosanoid syn-... 

Adenosine A1 Adenosine A2a Adenosine A3 aja-adrenoceptor ocib-adrenoceptor a2a-adrenoceptor a2b-adrenoceptor a -adrenoceptor Pi-adrenoceptor P2-adrenoceptor Angiotensin AT] Bradykinin B] Bradykinin B2 CGRP... 

Angiotensin converting enzyme (ACE) plays a central role in cardiovascular hemostasis. Its major function is the generation of angiotensin (ANG) II from ANGI and the degradation of bradykinin. Both peptides have profound impact on the cardiovascular system and beyond. ACE inhibitors are used to decrease blood pressure in hypertensive patients, to improve cardiac function, and to reduce work load of the heart in patients with cardiac failure. 

Effects of ACE Inhibitors Mediated by the Inhibition of Bradykinin Degradation... 

ACE inhibitors inhibit the degradation of bradykinin and potentiate the effects of bradykinin by about 50-100-fold. The prevention of bradykinin degradation by ACE inhibitors is particularly protective for the heart. Increased bradykinin levels prevent postischemic reperfusion arrhythmia, delays manifestations of cardiac ischemia, prevents platelet aggregation, and probably also reduces the degree of arteriosclerosis and the development of cardiac hypertrophy. The role of bradykinin and bradykinin-induced NO release for the improvement of cardiac functions by converting enzyme inhibitors has been demonstrated convincingly with use of a specific bradykinin receptor antagonist and inhibitors of NO-synthase. 

In the kidney, bradykinin increases renal blood flow, whereas glomerular filtration rate remains unaffected. 

Bradykinin stimulates natriuresis and, through stimulation of prostaglandin synthesis, inhibits the actions of antidiuretic hormone (ADH), thereby inhibiting water retention. Bradykinin further improves insulin sensitivity and cellular glucose utilization of skeletal muscle cells in experimental models. This, however, appears not to be relevant in the clinical context. 

Linz W, Martorana PA, Scholkens B (1990) Local inhibition of bradykinin degradation in ischemic hearts. J Cardiovasc Parmacol 15 S99-S109... 

The substrate specificity of ACE is low. ACE cleaves a variety of pairs of amino acids from the carboxy-terminal part of several peptide substrates. The conversion of ANGI to ANGII and the degradation of bradykinin to inactive fragments are considered the most important functions of ACE. Both peptides have profound impact on the cardiovascular system and beyond. ACE is thus an important target for ACE inhibitors. These compounds are frequently and efficiently used in the treatment of hypertension and cardiac failure. 

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