Janssen L J, Daniel E E
Department of Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
J Pharmacol Exp Ther. 1991 Feb;256(2):670-6.
Adrenoceptors mediating relaxant responses to exogenously added or endogenously released catecholamines in isolated canine bronchi (3rd-6th order) were characterized using selective beta receptor agonists and antagonists. Norepinephrine (3 x 10(7) to 3 x 10(-5) M) or isoproterenol (3 x 10(-8) to 10(-6) M) fully relaxed tissues precontracted with 3 x 10(-7) M carbachol (Cch). Salbutamol (Sal) also relaxed Cch-precontracted tissues, but this relaxant effect was extremely sensitive to the concentration of precontracting agent used: the maximal effect of Sal was 100, 79 and 28% reversal of tone in tissues precontracted with 2 x 10(-8), 10(-7) and 3 x 10(-7) M Cch. The effects of isoproterenol were antagonized by propranolol. Norepinephrine relaxations were antagonized by the beta-1-selective antagonist ICI 89,406 (pA2 = 7.70) and the beta-2-selective antagonist ICI 118,551 (pA2 = 6.33). Sal-relaxations were antagonized by ICI 118,551 (pA2 = 8.91). Field stimulation in tissues precontracted with McNeil A343 (M1-selective muscarinic agonist) produced transient relaxations which were antagonized by ICI 89,406 but not ICI 118,551 (both 10(-9) to 10(-7) M). Thus, exogenous and endogenous catecholamines relax canine bronchial smooth muscle by activating both beta-1 and beta-2 adrenoceptors, although the latter seen to play a significant role only when low concentrations of Cch were used.
利用选择性β受体激动剂和拮抗剂，对介导离体犬支气管（第3 - 6级）对外源性添加或内源性释放的儿茶酚胺产生舒张反应的肾上腺素能受体进行了表征。去甲肾上腺素（3×10⁻⁷至3×10⁻⁵M）或异丙肾上腺素（3×10⁻⁸至10⁻⁶M）可使预先用3×10⁻⁷M卡巴胆碱（Cch）预收缩的组织完全舒张。沙丁胺醇（Sal）也可使Cch预收缩的组织舒张，但这种舒张作用对所用预收缩剂的浓度极为敏感：在分别用2×10⁻⁸、10⁻⁷和3×10⁻⁷M Cch预收缩的组织中，Sal的最大舒张作用分别使肌张力逆转100%、79%和28%。异丙肾上腺素的作用被普萘洛尔拮抗。去甲肾上腺素引起的舒张被β₁选择性拮抗剂ICI 89,406（pA₂ = 7.70）和β₂选择性拮抗剂ICI 118,551（pA₂ = 6.33）拮抗。Sal引起的舒张被ICI 118,551（pA₂ = 8.91）拮抗。在用麦克尼尔A343（M₁选择性毒蕈碱激动剂）预收缩的组织中进行场刺激可产生短暂舒张，该舒张被ICI 89,406拮抗，但不被ICI 118,551（两者浓度均为10⁻⁹至10⁻⁷M）拮抗。因此，外源性和内源性儿茶酚胺通过激活β₁和β₂肾上腺素能受体使犬支气管平滑肌舒张，尽管只有在使用低浓度Cch时，后者似乎才起重要作用。
