Substance P: the relationship between receptor distribution in rat lung and the capacity of substance P to stimulate vascular permeability

The interaction of substance P (SP) with specific receptors in intact lung tissue was autoradiographically visualized, using slide-mounted tissue sections of rat lung tissue. SP receptors are highly concentrated in the central airways and are not detectable in peripheral bronchi, vessels, and alveoli. Within central airways, receptor distribution is most concentrated in the epithelium and small vessels in the lamina propria. Smooth muscle in airway or blood vessel walls expressed no detectable SP receptors. Immunohistochemical staining for SP revealed SP-containing nerves in the same areas where the receptors are localized. Displacement curves of SP bound to rat lung indicated that the C-terminal fragment was much more effective than the N-terminal fragment at competing for SP binding. Injection of 0.3 to 30 nmol/kg SP dramatically increased vascular permeability in the trachea and to a lesser extent in the hilus. Peripheral lung failed to respond to SP with increased vascular permeability unless toxic concentrations of SP were employed. SP increased the transudation of protein into the trachea within 5 min of injection, and the extravasated protein persisted through at least 2 h. Both SP and SP(3-11) were capable of stimulating increased vascular permeability, but SP(1-4) was inactive. SP caused mast cell degranulation as reflected in increased plasma histamine levels after SP or SP(3-11) injection, but SP(1-4) had no effect. In order to determine if histamine release caused by SP contributed to the vascular permeability response, the effects of H1 and H2 antihistamine treatment were studied.(ABSTRACT TRUNCATED AT 250 WORDS)