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

Catecholamines acting through the beta-adrenergic receptor (beta AR) c oupled-adenylylcyclase system stimulate a variety of responses by airw ay epithelial cells which affect airway caliber and the response to in flammatory stimuli. Although the tracheobronchial epithelium (TBE) is composed of several phenotypically differentiated cell types, surprisi ngly little is known about the expression of the beta AR system by the major subpopulations of TBE cells (i.e., basal and columnar). We, the refore, examined the function of the beta AR system in columnar and ba sal cell-enriched populations of rabbit tracheocytes. Cells were colle cted from 35 rabbits in 17 separate experiments and separated into bas al and columnar cell-enriched fractions by centrifugal elutriation. Th e columnar fraction demonstrated a significantly greater (P < 0.005) a denosine 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-enr iched 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, re spectively, P < 0.0001). However, when corrected for differences in ce ll size assessed from measurements of total cell protein, cAMP product ion per milligram protein and beta AR density per milligram protein we re 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 exp ressed 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 ce ll population does not. Conceivably the high density of beta AR on bas al cells suggests an important role of catecholamines in the regulatio n of basal cell proliferation.