通过阻断豚鼠肺动脉突触前β受体导致肾上腺素能传递失败。

Adrenergic transmission failure via the blockade of presynaptic beta receptors in guinea-pig pulmonary arteries.

作者信息

Misu Y, Kaiho M, Ogawa K, Kubo T

出版信息

J Pharmacol Exp Ther. 1981 Jul;218(1):242-7.

Abstract

Mechanisms related to the inhibitory actions of low concentrations of l- and d-propranolol on adrenergic transmission were investigated in isolated preparations of guinea-pig pulmonary arteries. In sympathetic nerve-radial muscle preparations, l-propranolol (3.3 X 10(-8) and 10(-7) M) dose-dependently inhibited by 15 to 20% contractile responses to nerve stimulation (1 Hz, 2-msec pulse width, 100-sec period and 30-min intervals) 30 and 60 min after the addition, whereas 3.3 X 10(-7) M produced a maximal inhibition. Contractile responses to cumulatively applied norepinephrine were not modified by pretreatment with l-propranolol (10(-7) - 10(-6) M). d-Propranolol (10(-7) M) produced no inhibition of adrenergic transmission. In superfused spiral preparations preloaded with [3H]norepinephrine, l-isoproterenol (3 X 10(-8) - 10(-6) M) dose-dependently facilitated total 3H efflux by transmural field stimulation by 10 to 35% under the same conditions; this facilitation was antagonized by l-propranolol (10(-7) M) but not by d-propranolol (10(-7) M). Phentolamine (3 X 10(-6) M) increased 3H efflux by approximately 3-fold. In the presence of phentolamine, l-propranolol (10(-7) M) significantly inhibited 3H efflux, whereas d-propranolol (10(-7) M) produced no effect. Presynaptic beta adrenoceptors are present on sympathetic nerve endings which innervate guinea-pig pulmonary arteries and low concentrations of propranolol inhibit adrenergic transmission via blockade of these receptors.

摘要

在豚鼠肺动脉的离体标本中，研究了低浓度左旋和右旋普萘洛尔对肾上腺素能传递的抑制作用机制。在交感神经-放射状肌标本中，加入左旋普萘洛尔（3.3×10⁻⁸和10⁻⁷M）后30和60分钟，对神经刺激（1Hz，2毫秒脉冲宽度，100秒周期和30分钟间隔）的收缩反应剂量依赖性地抑制15%至20%，而3.3×10⁻⁷M产生最大抑制。用左旋普萘洛尔（10⁻⁷ - 10⁻⁶M）预处理后，对累积应用去甲肾上腺素的收缩反应未改变。右旋普萘洛尔（10⁻⁷M）对肾上腺素能传递无抑制作用。在预先加载[³H]去甲肾上腺素的灌流螺旋标本中，在相同条件下，左旋异丙肾上腺素（3×10⁻⁸ - 10⁻⁶M）通过跨壁场刺激剂量依赖性地促进总³H流出10%至35%；这种促进作用被左旋普萘洛尔（10⁻⁷M）拮抗，但不被右旋普萘洛尔（10⁻⁷M）拮抗。酚妥拉明（3×10⁻⁶M）使³H流出增加约3倍。在酚妥拉明存在下，左旋普萘洛尔（10⁻⁷M）显著抑制³H流出，而右旋普萘洛尔（10⁻⁷M）无作用。突触前β肾上腺素能受体存在于支配豚鼠肺动脉的交感神经末梢上，低浓度的普萘洛尔通过阻断这些受体抑制肾上腺素能传递。