阿托品对离体兔海绵体松弛作用的作用机制。

Choi Y D, Chung W S, Choi H K

Department of Urology, Yonsei University College of Medicine, Seoul, Korea.

J Urol. 1999 Jun;161(6):1976-9.

PURPOSE

Atropine has been used to block cholinergic neurotransmission in basic research and has received recent interest clinically in the intracavernosal pharmacotherapy of erectile dysfunction. It has been suggested that at a low dose (10(-8) M), atropine blocks muscarinic receptors, and that at a large dose (10(-3) M), it induces the release of EDRF. However, no report has supported this idea experimentally. We tried to confirm the action of atropine in cavernosal tissue and define its mechanism.

MATERIALS AND METHODS

Strips of rabbit corpus cavernosum were mounted in organ chambers. On the precontracted muscle strips with phenylephrine (PHE; 5 x 10(-6) M), atropine was treated with increasing concentration from 10(-11) M. The relaxing activity of atropine was observed in deendothelialized tissue and preparation with treatment with methylene blue (10(-4) M), pyrogallol (10(-4) M), NW-nitro-L-arginine (L-NNA; 3 x 10(-4) M) and indomethacin (10(-4) M). To evaluate the relationship of atropine to Ca++, the muscle strip was incubated in Ca++ free solution, and Ca++ induced contraction by addition of CaCl2 (10(-3) M) was recorded with atropine. Depolarization by KCl was observed with atropine to investigate the relationship of atropine relaxation to K+.

RESULTS

On the precontracted muscle strip with PHE, atropine induced a dose-related contraction up to 10(-8) M and began to exert a relaxing effect at the concentration of 10(-7) M and reached the 93.6% relaxation effect at the concentration of 10(-4) M, causing dose-dependent relaxation. The relaxing effect of atropine was partially inhibited by endothelial disruption, and by pretreatment with methylene blue, pyrogallol, L-NNA, and indomethacin, although they were not statistically significant. At the basal state of muscle strips in Ca++ free solution, atropine decreased basal tension as well as inhibited the contraction induced by CaCl2 dose-dependently. However, atropine did not influence depolarization by KCl.

CONCLUSIONS

Atropine has both a contraction effect at lower concentrations and a relaxation effect at higher concentrations on cavernosal smooth muscle. It is presumed that the relaxation at higher concentrations is mediated via increasing intracellular calcium sequestration, not by hyperpolarization or secretion of EDRF.

目的

阿托品已用于基础研究中的胆碱能神经传递阻断，最近在勃起功能障碍的海绵体内药物治疗中受到临床关注。有人提出，低剂量（10⁻⁸ M）的阿托品可阻断毒蕈碱受体，而高剂量（10⁻³ M）时，它可诱导内皮舒张因子（EDRF）的释放。然而，尚无实验报告支持这一观点。我们试图证实阿托品在海绵体组织中的作用并确定其机制。

材料与方法

将兔海绵体条带安装在器官浴槽中。在去甲肾上腺素（PHE；5×10⁻⁶ M）预收缩的肌肉条带上，用浓度从10⁻¹¹ M递增的阿托品进行处理。在去内皮组织以及用亚甲蓝（10⁻⁴ M）、邻苯三酚（10⁻⁴ M）、Nω-硝基-L-精氨酸（L-NNA；3×10⁻⁴ M）和吲哚美辛（10⁻⁴ M）处理的制剂中观察阿托品的舒张活性。为了评估阿托品与钙离子的关系，将肌肉条带置于无钙溶液中孵育，加入氯化钙（10⁻³ M）诱导钙离子收缩，并记录阿托品存在时的情况。用阿托品观察氯化钾引起的去极化，以研究阿托品舒张与钾离子的关系。

结果

在PHE预收缩的肌肉条带上，阿托品在浓度达到10⁻⁸ M时诱导剂量相关的收缩，在10⁻⁷ M浓度时开始发挥舒张作用，在10⁻⁴ M浓度时达到93.6%的舒张效果，呈现剂量依赖性舒张。阿托品的舒张作用部分被内皮破坏以及亚甲蓝、邻苯三酚、L-NNA和吲哚美辛预处理所抑制，尽管差异无统计学意义。在无钙溶液中肌肉条带的基础状态下，阿托品可降低基础张力，并剂量依赖性地抑制氯化钙诱导的收缩。然而，阿托品不影响氯化钾引起的去极化。