DIFFERENTIAL INDUCTION OF FUNCTIONAL B1-BRADYKININ RECEPTORS ALONG THE RAT NEPHRON IN ENDOTOXIN-INDUCED INFLAMMATION

Background, Under physiological conditions, the effects of kinins in t he kidney are mainly mediated by the bradykinin B2-receptor, whereas t he kinin B1-receptor is strongly induced under inflammatory conditions in a variety of tissues. Knowledge of the distribution of the B1-rece ptor along the nephron is of importance since the B1-receptor might re place B2-receptors under these conditions. Methods. Using a RT-PCR/Sou thern blot approach allowing relative quantification of mRNA levels, t en different microdissected rat nephron segments were analyzed for the presence of the B1- and B2-receptor before and after endotoxin treatm ent to induce experimental inflammation, The functionality of the expr essed receptors was assessed by kinin-induced intracellular calcium ([ Ca2+](i)) mobilization in microdissected nephron segments. Results. Wh ile under physiological conditions no B1-receptor mRNA could be detect ed, after 18 hours of treatment with bacterial lipopolysaccharide (LPS ) the expression of B1-receptor mRNA was strongly induced in the effer ent arteriole, the medullary and inner medullary thin limb, and in the distal tubule. Moderate expression was found in the glomerulus, proxi mal convoluted and straight tubules, and in the medullary thick ascend ing limb. Small but detectable expression was observed in the cortical collecting duct. The induction of BI-receptor mRNA expression resulte d in functional receptor expression, since increases in [Ca2+](i) were observed upon B1-agonist stimulation. LPS treatment also increased th e expression of B2-receptor mRNA in all nephron segments except in the glomerulus, the inner medullary thin limb and the outer medullary col lecting duct. However, no related changes in B2-agonist induced rises in [Ca2+](i) were found. Conclusions. These studies show a functional induction of the B1-kinin receptor along the rat nephron, which should be taken in account to address the effects of kinins under inflammato ry conditions in the kidney.