Increased pulmonary α-adrenergic and reduced β-adrenergic receptors in experimental asthma

Abstract

The role of adrenergic mechanisms in the pathogenesis of asthma is controversial. Increased airways resistance in asthmatics is reversed by β-adrenergic receptor agonists such as isoprenaline, and it has been suggested that β-adrenergic activity is diminished in this condition¹. This is supported by studies showing reduced metabolic responses to β-adrenergic agonists^2,3 and fewer lymphocyte β-adrenergic receptors in asthmatics than in normal subjects⁴. However, the main contributory factor to diminished β-receptor responsiveness is probably a history of treatment with β-adrenergic agonists, resulting in tachyphylaxis^5,6. Nevertheless, similar but less pronounced changes have been observed in untreated asthmatic patients⁷, α-Adrenergic agonists produce bronchoconstriction in asthmatic patients, but not in normal subjects^8,9. Similarly, in vitro studies show α-adrenergic receptor-mediated constriction of bronchial smooth muscle from patients with increased airways resistance, but not from normal controls^10,11. In addition increased α-adrenergic receptor-mediated responses in vascular and pupillary smooth muscle have been reported in asthmatics¹². Using radioligand binding techniques, we have investigated the possibility that changes in numbers of α- and β-adrenergic receptors or their affinity are associated with the changes in adrenergic responsiveness observed in asthma. We report here that increased α- and fewer β-adrenergic receptors were observed in pulmonary homogenates of an animal model of chronic asthma than in those from controls.