EXPRESSION OF THE BETA-ADRENERGIC-RECEPTOR ADENYLYLCYCLASE SYSTEM IN BASAL AND COLUMNAR AIRWAY EPITHELIAL-CELLS

Catecholamines acting through the beta-adrenergic receptor (beta AR) coupled-adenylylcyclase system stimulate a variety of responses by airway epithelial cells which affect airway caliber and the response to inflammatory stimuli. Although the tracheobronchial epithelium (TBE) is composed of several phenotypically differentiated cell types, surprisingly little is known about the expression of the beta AR system by the major subpopulations of TBE cells (i.e., basal and columnar). We, therefore, examined the function of the beta AR system in columnar and basal cell-enriched populations of rabbit tracheocytes. Cells were collected from 35 rabbits in 17 separate experiments and separated into basal and columnar cell-enriched fractions by centrifugal elutriation. The columnar fraction demonstrated a significantly greater (P < 0.005) adenosine 3',5'-cyclic monophosphate (cAMP) response to isoproterenol (10(-9)-10(-5) M) than the basal cell-enriched fraction (i.e., 74.7 +/- 5.1 and 49.4 +/- 2.8 pmol/10(6) cells, in columnar and basal cell-enriched fractions, respectively, P < 0.0001) as well as a higher beta AR density (i.e., 8,678 +/- 840 and 4,754 +/- 406 beta AR sites/cell, respectively, P < 0.0001). However, when corrected for differences in cell size assessed from measurements of total cell protein, cAMP production per milligram protein and beta AR density per milligram protein were similar in the two cell fractions (P > 0.50 for both comparisons). beta AR subtype assessed by beta(1)AR and beta(2)AR subtype selective antagonists demonstrated that the beta(2)AR subtype predominated (i.e., > 90%) in both cell populations (P > 0.5). These data indicate that when corrected for differences in cell size, the beta AR system is expressed similarly in the columnar and basal airway epithelial subtypes. This finding is of interest, since columnar cells demonstrate highly differentiated functions which are under catecholamine control (e.g., salt and water secretion, mucociliary clearance), whereas the basal cell population does not. Conceivably the high density of beta AR on basal cells suggests an important role of catecholamines in the regulation of basal cell proliferation.