Effect of des arginine9-bradykinin and other bradykinin fragments on the synthesis of prostacyclin and the binding of bradykinin by vascular cells in culture

Abstract

Bradykinin (BK) fragments, des arg1-BK, des arg1,pro2-BK, des phe8,arg9-BK and des pro7,phe8,arg9-BK were synthesized and along with des arginine9-BK (daBK), tested for their ability to induce prostacyclin synthesis in homogeneous cultures of cells from the calf pulmonary artery. Of the fragments daBK was the only peptide, in addition to bradykinin (BK), to activate the synthesis of prostacyclin (PGI2) and platelet activating factor (PAF) in endothelial cells and PGI2 in fibroblasts and smooth muscle cells. Half-maximal activation of PGI2 synthesis differed with the cell type. The other fragments tested did not directly affect PGI2 synthesis. These fragments also did not inhibit daBK or BK activation of PG synthesis. BK bound to endothelial cells with a dissociation constant (Kd) of 2.1 nM and a Bmax of 47.9 fmoles/10(6) cells. The Kd for the binding of BK to smooth muscle cells and fibroblasts was somewhat higher, 4.9 nM and 7.9 nM, respectively. None of the fragments tested, including daBK, altered the binding of BK. Des arg9[leu8]-BK, reported to be a competitive antagonist of the bradykinin B1 receptor, inhibited daBK induced PG of PAF synthesis in endothelial cells but had little effect of BK binding or BK induced PG synthesis. Finally, the BK antagonist [thi5,8, d-phe7]-BK blocked both BK binding and the ability of either BK or daBK to induce PG synthesis, thus substantiating that the binding of these kinins is a step in the activation of PG synthesis.

Bradykinin potentiates insulin-stimulated glucose uptake and enhances insulin signal through the bradykinin B2 receptor in dog skeletal muscle and rat L6 myoblasts

“…The values of K d are within the range of those determined for bradykinin binding in a number of cell types (26)(27)(28)(29)(30). Moreover, a K d and a B max from our previous data in dog adipocytes (K d ¼ 83 pmol/l and B max ¼ 2.8 fmol/10 5 cells) are almost the same as those in dog skeletal muscle.…”

Sensory and Signaling Mechanisms of Bradykinin, Eicosanoids, Platelet-Activating Factor, and Nitric Oxide in Peripheral Nociceptors

“…The induction of B 1 receptor-mediated hyperalgesia was shown to depend on prostanoid formation in some studies (126,135,581). Consistent with this, B 1 receptor agonists were shown to increase the release of PGI 2 from various cell types (80,158,724).…”

Upregulation of B1 receptor mediating des‐Arg9‐BK‐induced rat paw oedema by systemic treatment with bacterial endotoxin

“…These results suggest that although histamine has an important role as an inflammatory mediator, it does not have the ability to potentiate kinin-mediated oedema formation. The potentiating effect of inflammatory mediators on the BR-mediated response of DABK in LPS-treated animals seems to involve B1 receptors, as revealed by the fact that the oedema elicited by coinjection of DABK together with each inflammatory mediator (Toda et al, 1987;Cahill et al, 1988;Galizzi et al, 1994) and interleukin-1 (IL-1) Lerner & Modeer, 1991). In addition, a synergism between DABK and IL-1 has been demonstrated to occur in increasing PGE2 formation in human gingival and synovial fibroblasts (Lerner & Modeer, 1991;Bathon et al, 1992;Lerner et al, 1992).…”