Chest, Vol 98, 376-381, Copyright © 1990 by American College of Chest Physicians

ARTICLES

Beta 2-adrenoceptors in human lung and peripheral mononuclear leukocytes of untreated and terbutaline-treated patients

RW Hauck, M Bohm, S Gengenbach, L Sunder-Plassmann, G Fruhmann and E Erdmann
Medizinische Klinik I, Universitat Munchen, West Germany.

Beta 2-adrenoceptor agonists act against bronchoconstriction by stimulating beta 2-adrenoceptors in bronchial smooth muscle. However, tachyphylaxis has been argued to occur because of beta 2-adrenoceptor down-regulation following therapy with beta 2-adrenergic agents. To investigate receptor alterations, human peripheral mononuclear leukocytes are frequently used, since human lung tissue is not easily available. In order to study whether beta 2-adrenoceptors in MNL reliably reflect the conditions in the human lung tissue, we compared MNL and human lung tissue of 18 patients who had to undergo lung resection. Ten patients were untreated, and eight had bronchodilator therapy prior to therapy with terbutaline because of bronchoconstriction. Both in human lung and MNL, the beta 2- adrenoceptor subpopulation was characterized by competition experiments with the beta 1-selective antagonist CGP 207.12 A and the beta 2- selective antagonist ICI 118.551. In MNL, a significant decrease in the density of beta 2-adrenoceptors was found in treated but not in untreated patients, while the antagonist affinity of the beta 2- adrenoceptors remained unchanged. However, in lung parenchyma, which was obtained at the very same time from the same patients, no down- regulation of the total amount of beta 2-adrenoceptors could be measured. It is concluded that MNLs are a reliable model for studying properties of beta 2-adrenoceptor regulation. However, the hereby obtained results show that MNLs do not reflect the conditions of beta 2- adrenoceptors in human lung tissue. Human lung tissue is found to be less susceptible than human MNL for beta 2-adrenoceptor down-regulation by terbutaline treatment at therapeutic doses.(ABSTRACT TRUNCATED AT 250 WORDS)

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