Thorin E
Institut de Cardiologie de Montréal, Centre de Recherche, Québec, Canada.
Br J Pharmacol. 1998 Nov;125(6):1188-93. doi: 10.1038/sj.bjp.0702199.
Interactions between two classes of receptors have been observed in several cell lines and preparations. The aim of this work was to assess the impact of simultaneous stimulation of endothelial muscarinic and alpha2-adrenergic receptors (alpha2-AR) on vascular reactivity. Rabbit middle cerebral arteries were isolated and changes in isometric tension were recorded in the presence of indomethacin. Inhibition of nitric oxide (NO) synthase with Nomega-nitro-L-arginine (L-NOARG, 100 micromol l(-1)) revealed alpha-AR-dependent contractions. Pre-addition of acetylcholine (ACH, 1 micromol l(-1)) augmented oxymetazoline (OXY, 10 micromol l(-1), alpha2-AR agonist)-, but decreased phenylephrine (PE, 10 micromol(-1), alpha1-AR agonist)-induced contraction (P<0.05). The effects of ACH were endothelium-dependent. Vessels were precontracted with 40 mmol l(-1) KCl-physiological salt solution (PSS) in the absence of L-NOARG, or PE or OXY in the presence of L-NOARG. In the presence of high external K+ or PE, ACH induced a potent relaxation (P<0.05). In the presence of OXY, however, ACH mediated contraction (P<0.05). After pertussis toxin (PTX, inactivator of Galpha(i/o) proteins) pre-treatment, alpha2-AR-dependent contractions were abolished. Forty mmol l(-1) KCl-PSS induced contraction was not altered by PTX whereas ACH-induced relaxation was augmented (P<0.05). To investigate if endothelin-1 (ET-1) intervened in the endothelium-dependent contractile response to ACH in the presence of OXY-dependent tone, vessels were incubated in the presence of BQ123 (1 micromol l(-1)), an ETA receptor antagonist. OXY-mediated tone was not affected by BQ123; however, ACH-induced contraction was reversed to a relaxation (P<0.05). These data indicate that activation of endothelial alpha2-AR triggers an endothelium-dependent, ET-1 mediated, contraction to ACH. This suggests that activation of alpha2-AR affects muscarinic receptor/G protein coupling leading to an opposite biological effect.
在几种细胞系和制剂中已观察到两类受体之间的相互作用。这项工作的目的是评估同时刺激内皮毒蕈碱受体和α2-肾上腺素能受体（α2-AR）对血管反应性的影响。分离兔大脑中动脉，并在吲哚美辛存在的情况下记录等长张力的变化。用Nω-硝基-L-精氨酸（L-NOARG，100 μmol l(-1)）抑制一氧化氮（NO）合酶可揭示α-AR依赖性收缩。预先添加乙酰胆碱（ACH，1 μmol l(-1)）可增强羟甲唑啉（OXY，10 μmol l(-1)，α2-AR激动剂）诱导的收缩，但可降低去氧肾上腺素（PE，10 μmol(-1)，α1-AR激动剂）诱导的收缩（P<0.05）。ACH的作用是内皮依赖性的。在不存在L-NOARG的情况下，用40 mmol l(-1) KCl-生理盐溶液（PSS）预收缩血管，或在存在L-NOARG的情况下用PE或OXY预收缩血管。在存在高细胞外K+或PE的情况下，ACH诱导强烈的舒张（P<0.05）。然而，在存在OXY的情况下，ACH介导收缩（P<0.05）。用百日咳毒素（PTX，Gα(i/o)蛋白的灭活剂）预处理后，α2-AR依赖性收缩被消除。40 mmol l(-1) KCl-PSS诱导的收缩不受PTX影响，而ACH诱导的舒张增强（P<0.05）。为了研究内皮素-1（ET-1）是否干预了在存在OXY依赖性张力的情况下对ACH的内皮依赖性收缩反应，将血管在ETA受体拮抗剂BQ123（1 μmol l(-1)）存在的情况下孵育。OXY介导的张力不受BQ123影响；然而，ACH诱导的收缩转变为舒张（P<0.05）。这些数据表明，内皮α2-AR的激活触发了对ACH的内皮依赖性、ET-1介导的收缩。这表明α2-AR的激活影响毒蕈碱受体/G蛋白偶联，导致相反的生物学效应。
