Up‐regulation of kinin B 1 receptor in the lung of streptozotocin‐diabetic rat: autoradiographic and functional evidence

The function and autoradiographic binding expression of kinin B 1 receptors were evaluated in the lungs of Streptozotocin (STZ)‐diabetic rats. The intrapleural injection (i.pl.) of des‐Arg 9 ‐bradykinin (des‐Arg 9 ‐BK) (50 and 100 nmol per site), a selective B 1 receptor agonist, increased time‐dependently the mononuclear and neutrophil cells influx in the pleural cavity of rats treated with STZ (65 mg kg −1 , i.p., 4 days earlier). This effect was significantly less in control rats. The influx of mononuclear and polymorphonuclear neutrophil cells induced by des‐Arg 9 ‐BK was significantly inhibited by two B 1 receptor antagonists (des‐Arg 10 ‐Hoe140 or R‐715, 100 nmol per site, 5 min earlier), but not by two B 2 receptor antagonists (Hoe140, 10 nmol or NPC 18884, 100 nmol per site, 5 min earlier). However, Hoe140 prevented the higher basal leukocyte influx seen in STZ‐diabetic rats. Leukocyte infiltration induced by des‐Arg 9 ‐BK in STZ‐diabetic rats was significantly reduced after treatment with insulin (2 U per day, s.c. over 4 days) or with an anti‐PMN antibody (0.1 ml of a 1 : 20 dilution, i.pl. 5 min earlier). Specific B 1 receptor binding sites were seen in lung sections from both control and STZ‐diabetic rats, yet the density of labelling was much greater in diabetic rats and particularly after intrapleural injection of des‐Arg 9 ‐BK. Treatment with insulin or with the anti‐PMN antibody markedly reduced B 1 receptor binding sites occurring after the injection of des‐Arg 9 ‐BK in STZ‐diabetic rats. Data suggest that the B 1 receptor is up‐regulated in the lungs of STZ‐diabetic rats, and its activation increases leukocyte infiltration into the pleural cavity. The overexpression of B 1 receptors seems to depend on neutrophils influx and appears to be associated with hyperglycaemia.British Journal of Pharmacology (2003) 138 , 13–22. doi: 10.1038/sj.bjp.0704999