Receptors in asthmatic airways.

Airway tissue obtained postmortem from nondiseased and severely asthmatic human lung was used in functional, radioligand binding and autoradiographic studies to investigate aspects of various receptor systems for putative mediators of asthma. Results indicate that asthma does not involve an intrinsic abnormality of smooth muscle contractility to spasmogens. Nor was there any evidence for up-regulation of histamine H1-receptor, muscarinic cholinoceptor, or alpha 1-adrenoceptor function. Conversely, severe asthma involving intense airway inflammation resulted in significant beta-adrenoceptor dysfunction, probably caused by receptor uncoupling from adenylate cyclase. Evidence was also obtained for histamine and methacholine-induced release of a nonprostanoid, airway epithelium-derived inhibitory factor (EpDIF), which may have a significant dilator effect in the adjacent bronchial circulation. The activity of this potentially protective inhibitory autacoid system would be expected to be reduced in asthma, which commonly involves epithelium damage. The autoradiographic distribution of specific binding sites for 125I-labeled substance P (I-SP) was also determined in bronchi from healthy humans and asthmatics. In sharp contrast to guinea pig airways where high levels of binding were detected over smooth muscle, specific I-SP binding was sparse over human airway smooth muscle from both sources, while dense binding was associated with structures immediately beneath the epithelium and with deep submucosal glands. These data suggest a more significant role for SP in secretory processes than in spasmogenic processes in human bronchi and highlight the potential for drawing invalid conclusions concerning human airway function from studies using animal models.