Up-regulation of kinin B1 receptor in the lung of streptozotocin-diabetic rat: autoradiographic and functional evidence.
1 The function and autoradiographic binding expression of kinin B(1) receptors were evaluated in the lungs of Streptozotocin (STZ)-diabetic rats. 2 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. 3 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. 4 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). 5 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. 6 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.[1]References
- Up-regulation of kinin B1 receptor in the lung of streptozotocin-diabetic rat: autoradiographic and functional evidence. Vianna, R.M., Ongali, B., Regoli, D., Calixto, J.B., Couture, R. Br. J. Pharmacol. (2003) [Pubmed]
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