Bradykinin receptor subtypes in rat lung: effect of interleukin-1 beta.

We have characterized bradykinin (BK) receptors in the rat lung and studied the effect of recombinant human interleukin-1 beta (IL-1 beta) on BK receptors in vitro and in vivo. In lung membranes, saturation studies with [3]BK revealed a single class of specific and saturable binding sites. The BK B1 antagonist des-Arg9[Leu8]-BK was less effective in displacing [3H]BK binding sites from lung membranes. In contrast, the selective BK B2 antagonists, Hoe 140 (D-Arg-[Hyp3,Thi5,D-Tic7,Oic8]-BK) and NPC 567 (D-Arg-[Hyp3,D-Phe7]-BK) fully inhibited the binding of [3H]BK to lung membranes with Ki values of 96.7 +/- 17.8 pM and 9.0 +/- 2.5 nM, respectively. Intratracheal administration of 500 U of IL-1 beta induced airway hyper-responsiveness to inhaled BK and neutrophilia in bronchoalveolar lavage fluid 18 to 24 hr later. Compared to naive or saline-treated animals, IL-1 beta had no effect on [3H]BK binding characteristics at 4, 12 or 24 hr after IL-1 beta administration. Twenty-four hours after IL-1 beta instillation, there was no change in the affinity of the selective BK B1 or B2 antagonists when compared to control animals. In vivo, the selective BK B2 receptor antagonists, NPC 567 (3 mumol kg-1 i.v.) and Hoe 140 (100 nmol kg-1 i.v.), inhibited BK-induced increase in lung resistance, whereas the selective BK B1 antagonist, des-Arg9[Leu8]-BK (10 mumol kg-1 i.v.), was without effect. These data suggest that the action of BK in the rat lung is dependent mainly on the activation of the BK B2 receptor subtype.(ABSTRACT TRUNCATED AT 250 WORDS)