Potentiation of bradykinin actions by analogues of the bradykinin potentiating nonapeptide BPP(9α)

Mueller, Sylvia; Gothe, Rita; Siems, Wolf-Dieter; Vietinghoff, Gabriele; Paegelow, Inge; Reissmann, Siegmund

Synthetic analogues of the bradykinin potentiating nonapeptide BPP(9α) indicate significantly different structural requirements for potentiation of the bradykinin (BK)-induced smooth muscle contraction (GPI) and the inhibition of isolated somatic angiotensin I-converting enzyme (ACE). The results disprove the ACE inhibition as the only single mechanism and also the direct interaction of potentiating peptides with the bradykinin receptors in transfected COS-7 cells as molecular mechanism of potentiation. Our results indicate a stimulation of inositol phosphates (IP(n)) formation independently from the B(2) receptor. Furthermore, the results with La(3+) support the role of extracellular Ca(2+) and its influx through corresponding channels. The missing effect of calyculin on the GPI disproves the role of phosphatases in the potentiating action. These experimental studies should not only contribute to a better understanding of the potentiating mechanisms but also incorporate a shift in the research towards the immune system, in particular towards the immunocompetent polymorphonuclear leukocytes. The chemotaxis of these cells can be potentiated most likely by exclusive inhibition of the enzymatic degradation of bradykinin. Thus the obtained results give evidence that the potentiation of the bradykinin action can occur by different mechanisms, depending on the system and on the applied potentiating factor.