β-adrenoceptor expression in different regions of human lung

L.J. Kay1, S.K. Suvarna3, R. Chess-Williams2 and P.T. Peachell1. 1Unit of Clinical Pharmacology and 2Department of Biomedical Science, University of Sheffield. 3Histopathology, Northern General Hospital, Sheffield.

Previous studies have shown that the predominant β-adrenoceptor subtype in human lung tissue is the β2-adrenoceptor (~80%) but β1-adrenoceptors are also present (~20%). Our own studies indicate a large difference in both b -adrenoceptor density and β2-adrenoceptor / β1-adrenoceptor splits among lung preparations. The aim of the present study was to determine whether the density and distribution of β-adrenoceptors differ in different regions of human lung.

Samples of human lung tissue were obtained following lobectomies and pneumonectomies. Saturation binding assays using 125I-iodocyanopindolol (0.03125 – 2 nM) were performed on membrane fractions of human lung tissue and specific binding was assessed using methods that have been described (Nishikawa et al., 1996). Discrimination of β2 -adrenoceptors and β1-adrenoceptors was determined using the selective β1-adrenoceptor antagonist, CGP20712A (0.01 μM 2-hydroxy-5-(2-(hydroxy-3-(4((1-methyl-4-trifluromethyl)-1-H-imidazol-2-yl)-phenoxy)-propyl)-aminoethoxyl)-benzamide). Data were analysed using GraphPad Prism software. Values are means ± s.e.m. and statistical significance was determined by ANOVA.

Binding assays were performed on membranes prepared from 43 lung samples. Total β-adrenoceptor densities ranged from 24 to 192 fmol mg-1 protein (mean ± s.e.m., 76.7 ± 5.6 fmol mg-1 protein) and the proportion of β2-adrenoceptors ranged from 80 to 100 % (mean ± s.e.m., 91 ± 0.1%). These lung samples were taken from peripheral regions of either upper, middle or lower lobes. In order to determine whether this variability in β-adrenoceptor density and distribution was due to the area of lung being sampled, binding assays were performed on tissue sampled from the periphery of upper, middle and lower lobes following pneumonectomies (n=4). The results obtained are shown in table 1.

TABLE 1

There was no difference statistically (P > 0.05) among regions of lung in either, (a) total β-adrenoceptor density, (b) β2-adrenoceptor density, or (c) β1-adrenoceptor density.

These findings suggest that although there is extensive inter-individual variability in b -adrenoceptor density and distribution, this does not seem to be influenced by the region of lung being sampled.

Nishikawa, M., et al., (1996). Eur. J. Pharmacol., 318, 123-129.