Gustafsson B, Persson C G
Department of Pharmacology, AB Draco, Lund, Sweden.
Thorax. 1991 May;46(5):360-5. doi: 10.1136/thx.46.5.360.
"Functional antagonism" is often used to describe the general relaxant effect of beta 2 agonists and xanthines and their ability to protect the airways against bronchoconstrictor stimuli. This study in guinea pig isolated trachea addresses the question of whether the capacity of these drugs to protect against constrictor stimuli is related to smooth muscle relaxation. Three antimuscarinic drugs were also examined to determine whether antagonism of mediators other than muscarinic agonists might contribute to bronchodilatation by these antimuscarinic drugs. Terbutaline (1.1 x 10(-7), 2.2 x 10(-7) M), theophylline (2.2 x 10(-4), 4.4 x 10(-4) M), and enprofylline (5.2 x 10(-5), 1.0 x 10(-4) M) relaxed the tracheal tension that remained after indomethacin treatment. They did not, however, alter the carbachol concentration-response curve significantly. In addition, neither theophylline (2.2 x 10(-4) M) nor terbutaline (1.1 x 10(-7) M) altered histamine induced contraction. Atropine sulphate, glycopyrrolate, and ipratropium bromide had EC50 values of 10(-9) - 10(-8) M for relaxation of carbachol induced contractions, whereas concentrations of 10(-6) - 10(-3) M or greater were required to relax contractions induced by allergen and nine other non-muscarinic mediators. It is suggested that bronchodilatation by antimuscarinic drugs in vivo is due to inhibition of acetylcholine induced bronchoconstriction alone and that beta 2 agonists and xanthines have poor ability to protect airway smooth muscle against constrictor stimuli. Hence mechanisms other than bronchodilatation and "functional antagonism" should be considered to explain the protection against constrictor stimuli in asthma seen with beta 2 agonists and xanthines.
“功能拮抗”常被用于描述β2激动剂和黄嘌呤类药物的一般舒张作用，以及它们保护气道免受支气管收缩刺激的能力。这项对豚鼠离体气管的研究探讨了这些药物预防收缩刺激的能力是否与平滑肌舒张有关。还研究了三种抗胆碱能药物，以确定除了抗胆碱能激动剂之外，对其他介质的拮抗作用是否可能有助于这些抗胆碱能药物的支气管扩张作用。特布他林（1.1×10⁻⁷、2.2×10⁻⁷M）、茶碱（2.2×10⁻⁴、4.4×10⁻⁴M）和恩丙茶碱（5.2×10⁻⁵、1.0×10⁻⁴M）可使吲哚美辛处理后残留的气管张力松弛。然而，它们并未显著改变卡巴胆碱浓度-反应曲线。此外，茶碱（2.2×10⁻⁴M）和特布他林（1.1×10⁻⁷M）均未改变组胺诱导的收缩。硫酸阿托品、格隆溴铵和异丙托溴铵对卡巴胆碱诱导的收缩松弛的EC50值为10⁻⁹ - 10⁻⁸M，而需要10⁻⁶ - 10⁻³M或更高的浓度才能松弛变应原和其他九种非胆碱能介质诱导的收缩。提示抗胆碱能药物在体内的支气管扩张作用仅归因于对乙酰胆碱诱导的支气管收缩的抑制，且β2激动剂和黄嘌呤类药物保护气道平滑肌免受收缩刺激的能力较差。因此，应考虑除支气管扩张和“功能拮抗”之外的机制来解释β2激动剂和黄嘌呤类药物在哮喘中对收缩刺激的保护作用。
