Mechanical and biochemical alterations in guinea-pig tracheae caused by sensitisation.
In order to test the hypothesis of beta-adrenergic receptor blockade in asthma bronchiale directly at the site of the asthmatic reaction, the tracheobronchial tree, we searched for mechanical and biochemical differences between isolated tracheae of actively sensitized and normal guinea pigs. The dose-response curves of terbutaline on isolated tracheae of actively sensitized guinea pigs were significantly shifted to the right in comparison with control trachea (ED50 11.8 X 10(-8) and 5.2 X 10(-8) M respectively). The sensitized organs dilated significantly slower than did controls (0.186 and 0.350 cm H2O/s, respectively) after addition of terbutaline, whereas the dilation velocity after addition of theophylline did not differ. The stimulation with fenoterol led to significantly lower amounts of cAMP in sensitized than in control tracheae (24.3 and 33.2 pmol/mg protein, respectively). The Km1 and Km2 of cAMP-phosphodiesterases of tracheal homogenates did not differ in both groups. Beta-adrenergic receptor binding studies with 3H-dihydro-alprenolol did not reveal a remarkable difference between sensitized and normal tracheae. The results indicate, that sensitization led to a partial blockade of the beta-adrenergic receptor adenylatecyclase system. However, the exact site of this effect remains obscure.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001249:Asthma / Q000503:physiopathology*; D001980:Bronchi / Q000294:innervation*; D000242:Cyclic AMP / Q000378:metabolism; D004082:Dihydroalprenolol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D007700:Kinetics; D009130:Muscle, Smooth / Q000294:innervation; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D012130:Respiratory Hypersensitivity / Q000503:physiopathology*; D013726:Terbutaline / Q000494:pharmacology; D014132:Trachea / Q000294:innervation*
D011943:Receptors, Adrenergic, beta; D004082:Dihydroalprenolol; D006632:Histamine; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D013726:Terbutaline