Hypothesized and found mechanisms for potentiation of bradykinin actions

Abstract

Potentiation of hormone actions can occur by different mechanisms, including inhibition of degrading enzymes, interaction with the hormone receptor leading to stabilization of bioactive conformation or leading to receptor homo-and hetero-oligomerization, receptor phosphorylation and dephosphorylation or can occur by directly influencing the signal transduction and ion channels. In this review the potentiation of bradykinin actions in different systems by certain compounds will be reviewed. Despite many long years of experimental research and investigation the mechanisms of potentiating action remain not fully understood. One of the most contradictory findings are the distinct differences between the inhibition of the angiotensin I-converting enzyme and the potentiation of the bradykinin induced smooth muscle reaction. Contradictory findings and hypothesized mechanisms in the literature are discussed in this review and in some cases compared to own results. Investigation of potentiating actions was extended from hypotension, smooth muscle reaction and cellular actions to activation of immunocompetent cells. In our opinion the potentiation of bradykinin action can occur by different mechanisms, depending on the system and the applied potentiating factor used.Hormone actions can be potentiated by different factors interacting with the receptor, by enzymatic degradation or by signal pathways. However the entire overall process has been studied in detail for only very few hormones [1][2][3]. For therapeutically used hormones this knowledge about potentiating compounds and their action mechan-

Do the Cardiovascular Effects of Angiotensin-Converting Enzyme (ACE) I Involve ACE-Independent Mechanisms? New Insights from Proline-Rich Peptides ofBothrops jararaca

“…Likewise, there are scarce but consistent reports showing that ACEI can produce vasodilation by mechanism that can- not be ascribed to ACE inhibition (Marks et al, 1980;Antonaccio et al, 1979;Mittra and Singh, 1998;Houben et al, 2000;Mueller et al, 2006). For example, Houben et al (2000) have found that quinaprilat but not enaprilat produced significant vasodilation with 15 min of administration.…”

“…Bradykinin potentiation by ACEI might involve beside ACE inhibition, induction of a cross-talk mechanism between ACE and B 2 receptors (Mittra and Singh, 1998;Marcic et al, 1999;Houben et al, 2000;Mueller et al, 2006). Indeed, more than 30 years ago, an ACE-independent mechanism for BK potentiation by ACEI of B. jararaca venom was suggested (Camargo and Ferreira, 1971;Greene et al, 1972).…”

“…It has been suggested that Bj-BPPs may act by an ACEindependent mechanism (Camargo and Ferreira, 1971;Greene et al, 1972;Mueller et al, 2005Mueller et al, , 2006. A similar possibility has been raised for conventional ACEI (Marks et al, 1980;Mittra and Singh, 1998;Houben et al, 2000;Ignjatovic et al, 2002).…”

Bj-PRO-5a, a natural angiotensin-converting enzyme inhibitor, promotes vasodilatation mediated by both bradykinin B2 and M1 muscarinic acetylcholine receptors

“…Recently published works have suggested that the mechanism responsible for the enhancement of BK activity by Bj-PROs cannot be entirely explained by the inhibition of ACE enzymatic activity [9,23,32,33]. Furthermore, ACE inhibition as the only explanation for the antihypertensive effects caused by inhibitory molecules of this enzyme has been challenged in the literature [34][35][36][37][38]. Thus, the hypothesis was raised that each Bj-PRO might act through distinct mechanism of action, probably involving different target proteins [9,23].…”

Biology of Peptides

“…The B 1 receptor, mainly involved in inflammatory processes, binds [des-Arg 9 ]bradykinin more strongly than bradykinin, whereas the B 2 receptor shows a greater affinity to the native hormone. Bradykinin-potentiating peptides (BPP) are peptides of different structure and from different natural sources, which are able to potentiate the bradykinin actions in various systems [274]. Enzymatically stable agonists for the B 2 receptor are potential therapeutics for infarct treatment, whereas antagonists of bradykinin are potential agents for the treatment of inflammation.…”