异丙肾上腺素对猫气管收缩-舒张周期的影响。
Effects of isoprenaline on the contraction-relaxation cycle in the cat trachea.
作者信息
Ito Y, Itoh T
出版信息
Br J Pharmacol. 1984 Nov;83(3):677-86. doi: 10.1111/j.1476-5381.1984.tb16221.x.
Effects of isoprenaline (Isop) on the contractile properties of the smooth muscle cells of cat trachea were investigated using intact and chemically skinned muscle preparations and an isometric tension recording method. In the intact muscle preparations, Isop 3 X 10(-10) or 3 X 10(-9) M significantly suppressed the amplitude of tonic contractions evoked by acetylcholine (ACh) 10(-7) M or 10(-5) M, respectively. Following treatment of the tissue with Ca2+-free 2 mM EGTA-containing solution after depletion of stored Ca2+ with caffeine, 2.5 mM Ca2+ was applied for 5 min (procedure 1), and subsequently 10 mM caffeine was applied in Ca2+-free 2 mM EGTA containing solution. The object was to estimate the amount of stored Ca2+ during procedure 1 from the amplitude of the caffeine (10 mM)-induced contraction (procedure 2). Isop, applied during procedure 1, did not affect the amplitude of the caffeine-induced contraction; however, when applied during procedure 2, this agent (10(-8)M) significantly suppressed the amplitude of the caffeine-induced contraction to about 90% of the control value. ACh (10(-5)M), applied during procedure 1, evoked phasic and tonic contractions. Isop (10(-8)M), applied simultaneously with ACh (10(-5)M), suppressed the amplitude of the ACh-induced contraction yet increased the amplitude of contraction evoked by the subsequent application of caffeine 10 mM (procedure 2). Effects of conditioning application of ACh (10(-7) or 10(-5)M) on the caffeine-induced contraction were observed in the presence or absence of Isop during procedure 2. When ACh 10(-5)M was used, subsequent application of caffeine 10 mM evoked no mechanical response, in control conditions. However, after the pretreatment of the tissue with Isop during procedure 2, the amplitude of the ACh (10(-5)M)-induced contraction was not affected, yet the subsequent application of caffeine (10 mM) evoked minute but discrete contractions, indicating that Isop did enhance the sequestration of free Ca2+ into the storage sites. In the saponin-treated skinned muscles, the minimum concentration of Ca2+ required to produce contraction was 1 X 10(-7)M, and the maximum contraction was obtained with 1 X 10(-5)M Ca2+. Isop (10(-6)M) had no effect on the relationship between free-Ca2+ and the amplitude of the contraction. However, simultaneous application of high concentrations of cyclic AMP (10(-4)M) and cyclic AMP-dependent protein kinase (50 micrograms ml-1) significantly suppressed contractions evoked by 3 X 10(-7) or 10(-5)M Ca2+. 8 These results indicate that Isop suppresses the contraction evoked by various agonists in the cat trachea, mainly through sequestration of Ca2+ into the intracellular storage sites, rather than by direct or indirect (through cyclic AMP) actions on the contractile proteins.
采用完整和化学去膜的肌肉标本以及等长张力记录方法，研究了异丙肾上腺素（Isop）对猫气管平滑肌细胞收缩特性的影响。在完整肌肉标本中，3×10⁻¹⁰或3×10⁻⁹M的Isop分别显著抑制了由10⁻⁷或10⁻⁵M乙酰胆碱（ACh）诱发的强直收缩幅度。在用咖啡因耗尽储存的Ca²⁺后，用含2 mM EGTA的无Ca²⁺溶液处理组织，然后施加2.5 mM Ca²⁺ 5分钟（步骤1），随后在含2 mM EGTA的无Ca²⁺溶液中施加10 mM咖啡因。目的是根据咖啡因（10 mM）诱发收缩的幅度来估计步骤1期间储存的Ca²⁺量（步骤2）。在步骤1期间施加的Isop不影响咖啡因诱发收缩的幅度；然而，在步骤2期间施加时，该药物（10⁻⁸M）显著将咖啡因诱发收缩的幅度抑制至对照值的约90%。在步骤1期间施加的ACh（10⁻⁵M）诱发了相位和强直收缩。与ACh（10⁻⁵M）同时施加的Isop（10⁻⁸M）抑制了ACh诱发收缩的幅度，但增加了随后施加10 mM咖啡因（步骤2）诱发收缩的幅度。在步骤2期间，观察了预处理ACh（10⁻⁷或10⁻⁵M）对咖啡因诱发收缩的影响，有无Isop存在。在对照条件下，当使用10⁻⁵M ACh时，随后施加10 mM咖啡因未诱发机械反应。然而，在步骤2期间用Isop预处理组织后，ACh（10⁻⁵M）诱发收缩的幅度未受影响，但随后施加咖啡因（10 mM）诱发了微小但离散的收缩，表明Isop确实增强了游离Ca²⁺向储存位点的隔离。在皂素处理的去膜肌肉中，产生收缩所需的Ca²⁺最低浓度为1×10⁻⁷M，用1×10⁻⁵M Ca²⁺可获得最大收缩。Isop（10⁻⁶M）对游离Ca²⁺与收缩幅度之间的关系无影响。然而，同时施加高浓度的环磷酸腺苷（10⁻⁴M）和环磷酸腺苷依赖性蛋白激酶（50微克/毫升）显著抑制了由3×10⁻⁷或10⁻⁵M Ca²⁺诱发的收缩。这些结果表明，Isop主要通过将Ca²⁺隔离到细胞内储存位点来抑制猫气管中各种激动剂诱发的收缩，而不是通过对收缩蛋白的直接或间接（通过环磷酸腺苷）作用。
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