β2-Adrenoceptors in Human Lung and Peripheral Mononuclear Leukocytes of Untreated and Terbutaline-treated Patients

β-adrenoceptor agonists act against bronchoconstriction by stimulating β2-adrenoceptors in bronchial smooth muscle. However, tachyphylaxis has been argued to occur because of β2-adrenoceptor down-regulation following therapy with β2-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 β2-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 β2-adrenoceptor subpopulation was characterized by competition experiments with the β1-selective antagonist CGP 207.12 A and the β2-selective antagonist ICI 118.551. In MNL, a significant decrease in the density of β2-adrenoceptors was found in treated but not in untreated patients, while the antagonist affinity of the β2-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 β2-adrenoceptors could be measured. It is concluded that MNLs are a reliable model for studying properties of β2-adrenoceptor regulation. However, the hereby obtained results show that MNLs do not reflect the conditions of β2-adrenoceptors in human lung tissue. Human lung tissue is found to be less susceptible than human MNL for β2-adrenoceptor down-regulation by terbutaline treatment at therapeutic doses. The lack of β2-adrenoceptor down-regulation provides a biochemical explanation for the preserved efficacy of β2-sympathomimetics after long-term antiasthmatic treatment.