u-44069 and icatibant

The effect of bradykinin (BK) on the contraction of rat mesangial cells (MC) was compared with that of various vasoactive agents. BK induced a dose-dependent contraction [one-half maximal effective dose (ED50) = 50 nM] inhibited by the B2 antagonist, HOE-140 (ED50 = 10 nM). BK-induced MC contraction was independent of extracellular calcium and was reduced by inhibition of protein kinase C (PKC). Neomycin completely prevented the increase in intracellular calcium and the formation of inositol 1,4,5-trisphosphate induced by BK but only reduced cell contraction. Inhibition of prostaglandin (PG) formation and administration of the endoperoxide antagonist SQ-27427 also partly decreased the effect of BK. Interestingly, only the addition of both neomycin and mepacrine resulted in a complete inhibition of cell contraction. These results suggest that BK, via a B2-kinin receptor, induces contraction of MC through two distinct mechanisms, one associated to the phospholipase C pathway and subsequent activation of PKC and the second one dependent on PG formation. These in vitro effects may be relevant in explaining the effects of BK and converting enzyme inhibitors on glomerular hemodynamics.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Adrenergic beta-2 Receptor Antagonists; Angiotensin II; Animals; Arginine Vasopressin; Bombesin; Bradykinin; Bridged Bicyclo Compounds; Bridged Bicyclo Compounds, Heterocyclic; Cell Membrane; Cells, Cultured; Dinoprost; Dinoprostone; Dose-Response Relationship, Drug; Endothelins; Fatty Acids, Unsaturated; Glomerular Mesangium; Indomethacin; Kinetics; Naphthalenes; Neomycin; Polycyclic Compounds; Prostaglandin Endoperoxides, Synthetic; Protein Kinase C; Quinacrine; Rats; Receptors, Adrenergic, beta-2; Surface Properties; Tetradecanoylphorbol Acetate; Thromboxane A2; Vasoconstrictor Agents