[Adrenergic and purinergic receptors and bronchial motoricity]

Numerous studies have been, and are being devoted to the nature of adrenergic and purinergic receptors in the bronchopulmonary system. Studies of beta-adrenoceptors performed with ligands (table I) have demonstrated the presence of two types of receptors, beta 1 and beta 2 in proportions of about 15 : 100 respectively; this proportion is approximately the same at all levels of the tracheobronchial tree. Beta-adrenoceptors (beta 1 + beta 2) are globally more numerous in peripheral organs which contain heterogeneous tissues. Their number can be modified in certain circumstances, notably in asthma, infection and after prolonged treatment with sympathomimetic amines. Functional studies using specific beta 1-adrenoceptor agonists (RO-363 or prenalterol) or determining the relative activities of beta 1 and/or beta 2 stimulants and their inhibition by selective beta-blockers have shown that stimulation of beta 1-adrenoceptors may produce partial relaxation of the isolated trachea but not of lung parenchyma, the latter being supposed to represent distal airways. Studies on isolated small bronchi, about 0.1 mm in diameter (fig. 1 and 2A) have confirmed that stimulation of beta 1-adrenoceptors has not effect on distal airways. They have also demonstrated that beta 2-stimulants have different intrinsic activities (fig. 2B). Studies of alpha-adrenergic receptors using ligands (table II) have shown that these receptors are in small number in the tracheobronchial tree of numerous animal species. Functional studies on the conscious guinea-pig have shown that clonidine can potentiate the bronchoconstrictor effects of acetylcholine, histamine and serotonin (fig. 3) and that this potentiating effect is specifically inhibited by yohimbine and piperoxan (fig. 4). This action of clonidine has been attributed to depression of the reflex sympathetic activity associated with bronchospasm. Alpha 1-adrenoceptor agonists (phenylephrine, methoxamine) induce contracture of the isolated bronchial smooth muscle (fig. 5) but may partially reduce the bronchoconstrictor effects of acetylcholine, histamine or serotonin (fig. 6). This last effect is partially inhibited by alpha 1-blockers (fig. 7) and seems to be due to shrinkage of the bronchial mucosa. Finally, studies of purinergic receptors in the bronchopulmonary system have shown that they probably are of the A2-P1 type (tables III and IV) and that they do not seem to be involved in the bronchodilator activity of theophylline.