Mukherjee A, Wasserman M A
Methods Find Exp Clin Pharmacol. 1986 Nov;8(11):667-73.
An imbalance between the density of alpha- and beta-adrenergic receptors in airway smooth muscle has been suggested as one of the potential underlying mechanisms of bronchial asthma. Therefore, the present study was conducted to examine the presence and functional behavior of alpha-adrenoceptors in isolated human bronchi and bronchioles. Human airway tissues did not show any spontaneous tone during equilibration in physiological solution. Sensitivity of non-cartilaginous airways (8th generation and smaller) to histamine was approximately 3 times more than cartilaginous (2nd-7th generation) airways. In the presence of beta-adrenoceptor blockade, norepinephrine (3 X 10(-4) M) evoked approximately 14-40% of maximum histamine contraction in cartilaginous and non-cartilaginous airways from three donors. When tone in these tissues was elevated by pretreatment with histamine (10(-5) M), leukotriene D4 (10(-10) M), carbachol (1 X 10(-6) M-3 X 10(-6) M) or KCl (10(-2) M), the sensitivity to norepinephrine was potentiated. Airway tissue from one donor was found to be highly reactive to norepinephrine and the maximum contractions were 118 and 145% of maximum histamine contraction for cartilaginous and non-cartilaginous airways, respectively. Time to reach maximum contraction in cartilaginous airways was 80 min compared to 21 min for non-cartilaginous airways from the same donor. These data suggest that human airways contain contractile alpha-adrenoceptors in addition to relaxant beta-adrenoceptors, which haven been reported previously in the literature. Though activation of alpha-adrenoceptors induces contractions in human airway smooth muscle, the potency of norepinephrine for alpha-adrenoceptors in these airways is low compared to that reported for vascular smooth muscle.
气道平滑肌中α-和β-肾上腺素能受体密度的失衡被认为是支气管哮喘潜在的发病机制之一。因此，本研究旨在检测人离体支气管和细支气管中α-肾上腺素能受体的存在情况及其功能特性。在生理溶液中平衡时，人气道组织未表现出任何自发张力。非软骨气道（第8代及更小气道）对组胺的敏感性约为软骨气道（第2 - 7代）的3倍。在β-肾上腺素能受体被阻断的情况下，去甲肾上腺素（3×10⁻⁴ M）在来自三名供体的软骨和非软骨气道中诱发了约14% - 40%的组胺最大收缩反应。当用组胺（10⁻⁵ M）、白三烯D4（10⁻¹⁰ M）、卡巴胆碱（1×10⁻⁶ M - 3×10⁻⁶ M）或氯化钾（10⁻² M）预处理使这些组织的张力升高时，对去甲肾上腺素的敏感性增强。发现一名供体的气道组织对去甲肾上腺素高度敏感，软骨气道和非软骨气道的最大收缩分别为组胺最大收缩的118%和145%。同一供体的软骨气道达到最大收缩的时间为80分钟，而非软骨气道为21分钟。这些数据表明，除了文献中先前报道的舒张性β-肾上腺素能受体外，人气道还含有收缩性α-肾上腺素能受体。尽管α-肾上腺素能受体的激活会诱导人气道平滑肌收缩，但与血管平滑肌相比，这些气道中去甲肾上腺素对α-肾上腺素能受体的效力较低。
