Autoradiographic visualization of bradykinin receptors in human and guinea pig lung.

High affinity [3H]bradykinin (BK) receptor binding sites have been identified in human and guinea pig lung sections by in vitro autoradiography. [3H]BK was incubated with tissue sections for 120 min at 25 degrees C and non-specific binding determined by incubating adjacent serial sections in the presence of unlabelled BK. In saturation experiments with guinea pig lung sections, a single class of high affinity binding sites was identified with an apparent dissociation constant (Kd) of 0.5 +/- 0.1 nM and a maximal binding capacity (Bmax) of 35.2 +/- 2.9 fmol/mg protein (n = 5). The binding of [3H]BK was inhibited by unlabelled BK and NPC 349 (a specific B2 antagonist) at IC50 of 2.7 +/- 0.4 and 87 +/- 9 nM (n = 3), respectively. In contrast, no inhibition was found at 1 microM for a variety of vasoactive peptides such substance P, calcitonin gene-related peptide, vasoactive intestinal peptide and des-Arg9-[Leu8]BK (a specific B1-antagonist). Autoradiography revealed that BK receptors were widely distributed in human and guinea pig lung, with dense labelling over bronchial and pulmonary blood vessels of all sizes and in the lamina propria immediately subjacent to the basal epithelial cell layer in large airways. Airway smooth muscle was sparsely labelled in large airways, but greater labelling in smaller airways. There was also detectable labelling over submucosal glands and nerve fibres in human intrapulmonary bronchi and over alveolar walls in both species. The high density of BK receptors on bronchial and pulmonary blood vessels indicate that BK may play an important role in the regulation of airway and pulmonary blood flow, as well as airway epithelial regulation.