Autoradiographic visualization of beta-adrenoceptor subtypes in human lung.

Adrenoceptor subtypes have been localized in human lung by an autoradiographic method, using [125I]iodocyanopindolol (ICYP) to label beta-receptors in tissue sections. The ICYP was incubated with cryostat sections of microscopically normal human lung method on microscope slides for 2 h at 37 degrees C. Nonspecific binding was determined by incubating adjacent serial sections in the presence of 200 microM (-)-isoproterenol. Specific binding, which accounted for greater than 90% of total counts bound to the sections, was saturable, of high affinity, and stereoselective, having the same pharmacologic characteristics as binding to homogenates prepared from the same lungs. Competition with selective beta-receptor antagonists ICI 118,551 (beta 2-selective) and betaxolol (beta 1-selective) showed that the ratio of beta 2 to beta 1-receptors in the sections was approximately 3:1. Autoradiography revealed that beta-receptors were widely distributed, with dense labeling over airway epithelium, alveolar walls, and submucosal glands, and a lower density of grains over airway and vascular smooth muscle. The beta-receptors of airway smooth muscle from large and small airways were entirely of the beta 2-receptor subtype, which is consistent with functional studies. Similarly, beta-receptors of airway epithelium and vascular smooth muscle were also entirely of the beta 2-receptor subtype. In bronchial submucosal glands and alveolar walls, both receptor subtypes appeared to coexist with beta 2-receptors, making up 10% of the total in glands and 30% in alveoli. The significance of beta 1- and beta 2-receptors in alveolar walls (which account for greater than 90% of total beta-receptors in human lung) remains to be determined.