{"title":"cAMP和β-肾上腺素受体参与黄酮类化合物对大鼠子宫平滑肌的松弛作用","authors":"M. P. Revuelta, A. Hidalgo, B. Cantabrana","doi":"10.1111/j.1365-2680.1999.tb00008.x","DOIUrl":null,"url":null,"abstract":"<div>\n \n <p><b>1</b> The effect of the flavonoids genistein (3–100 μM), kaempferol (3–60 μM) and quercetin (1–100 μM) on KCI (60 mM)-induced tonic contraction in rat smooth muscle was assayed. In the same way, the modification of these effects in the presence of an inhibitor of protein kinase (PKA) (Rp-cAMPS), an inhibitor of phosphodiesterase (papaverine) and β-adrenoreceptor blocking agents (propranolol and atenolol) was studied.</p>\n <p><b>2</b> The flavonoids totally relaxed the KCI-induced tonic contraction (IC<sub>50</sub>: genistein 20.2 ± 2.0 μM, <i>n</i> = 11; kaempferol 10.1 ± 1.6 μM, <i>n</i> = 8; quercetin 13.2 ± 1.2 μM, <i>n</i> = 8).</p>\n <p><b>3</b> The incubation with Rp-cAMPS (10 and 100 μM) 30 min prior to KCI shifted the dose-response curve of the flavonoids to the right, increasing their IC<sub>50</sub> up to 27.8 ± 3.8 and 31.9 ± 7.3 μM, respectively, for genistein; 24.7 ± 0.2 and 19.6 ± 4.9 μM, respectively, for kaempferol; 18.8 ± 2.2 and 18.4 ± 1.5 μM, respectively, for quercetin.</p>\n <p><b>4</b> Papaverine (3–100 μM) also relaxed the contraction induced by KCI and this effect was significantly displaced to the right with Rp-cAMPS (10 μM) (IC<sub>50</sub> 12.1 ± 2.2 vs. 16.5 ± 3.1 μM). Papaverine (3 μM) added to the organ bath 15 min before the contractile agent increased the relaxing effect of the flavonoids and significantly decreased their IC<sub>50</sub> (genistein 20.2 ± 2.0 vs. 9.8 ± 1.4 μM; kaempferol 10.1 ± 1.6 vs. 6.6 ± 0.7 μM; quercetin 13.2 ± 1.2 vs. 7.8 ± 1.4 μM).</p>\n <p><b>5</b> The incubation with atenolol (10 μM) did not alter the relaxing effect of the flavonoids. In the same experimental conditions, propranolol (10 μM) did not modify the effect of genistein and kaempferol, but shifted the response curve of quercetin significantly to the right (13.2 ± 1.2 vs. 17.7 ± 3.4 μM).</p>\n <p><b>6</b> The results suggest that genistein, kaempferol and quercetin produced the relaxation of uterine smooth muscle by increasing intracellular cAMP. β-Adrenoceptors could also be involved in the effect of quercetin.</p>\n </div>","PeriodicalId":100151,"journal":{"name":"Autonomic and Autacoid Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2009-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1365-2680.1999.tb00008.x","citationCount":"29","resultStr":"{\"title\":\"Involvement of cAMP and β-adrenoceptors in the relaxing effect elicited by flavonoids on rat uterine smooth muscle\",\"authors\":\"M. P. Revuelta, A. Hidalgo, B. Cantabrana\",\"doi\":\"10.1111/j.1365-2680.1999.tb00008.x\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n <p><b>1</b> The effect of the flavonoids genistein (3–100 μM), kaempferol (3–60 μM) and quercetin (1–100 μM) on KCI (60 mM)-induced tonic contraction in rat smooth muscle was assayed. In the same way, the modification of these effects in the presence of an inhibitor of protein kinase (PKA) (Rp-cAMPS), an inhibitor of phosphodiesterase (papaverine) and β-adrenoreceptor blocking agents (propranolol and atenolol) was studied.</p>\\n <p><b>2</b> The flavonoids totally relaxed the KCI-induced tonic contraction (IC<sub>50</sub>: genistein 20.2 ± 2.0 μM, <i>n</i> = 11; kaempferol 10.1 ± 1.6 μM, <i>n</i> = 8; quercetin 13.2 ± 1.2 μM, <i>n</i> = 8).</p>\\n <p><b>3</b> The incubation with Rp-cAMPS (10 and 100 μM) 30 min prior to KCI shifted the dose-response curve of the flavonoids to the right, increasing their IC<sub>50</sub> up to 27.8 ± 3.8 and 31.9 ± 7.3 μM, respectively, for genistein; 24.7 ± 0.2 and 19.6 ± 4.9 μM, respectively, for kaempferol; 18.8 ± 2.2 and 18.4 ± 1.5 μM, respectively, for quercetin.</p>\\n <p><b>4</b> Papaverine (3–100 μM) also relaxed the contraction induced by KCI and this effect was significantly displaced to the right with Rp-cAMPS (10 μM) (IC<sub>50</sub> 12.1 ± 2.2 vs. 16.5 ± 3.1 μM). Papaverine (3 μM) added to the organ bath 15 min before the contractile agent increased the relaxing effect of the flavonoids and significantly decreased their IC<sub>50</sub> (genistein 20.2 ± 2.0 vs. 9.8 ± 1.4 μM; kaempferol 10.1 ± 1.6 vs. 6.6 ± 0.7 μM; quercetin 13.2 ± 1.2 vs. 7.8 ± 1.4 μM).</p>\\n <p><b>5</b> The incubation with atenolol (10 μM) did not alter the relaxing effect of the flavonoids. In the same experimental conditions, propranolol (10 μM) did not modify the effect of genistein and kaempferol, but shifted the response curve of quercetin significantly to the right (13.2 ± 1.2 vs. 17.7 ± 3.4 μM).</p>\\n <p><b>6</b> The results suggest that genistein, kaempferol and quercetin produced the relaxation of uterine smooth muscle by increasing intracellular cAMP. β-Adrenoceptors could also be involved in the effect of quercetin.</p>\\n </div>\",\"PeriodicalId\":100151,\"journal\":{\"name\":\"Autonomic and Autacoid Pharmacology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2009-01-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1111/j.1365-2680.1999.tb00008.x\",\"citationCount\":\"29\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Autonomic and Autacoid Pharmacology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2680.1999.tb00008.x\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Autonomic and Autacoid Pharmacology","FirstCategoryId":"1085","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2680.1999.tb00008.x","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 29
摘要
1观察黄酮染料木素(3 ~ 100 μM)、山奈酚(3 ~ 60 μM)、槲皮素(1 ~ 100 μM)对KCI (60 mM)致大鼠平滑肌强直收缩的影响。以同样的方式,研究了蛋白激酶抑制剂(PKA) (Rp-cAMPS)、磷酸二酯酶抑制剂(罂粟碱)和β-肾上腺素受体阻滞剂(心得安和阿替洛尔)存在时对这些作用的修饰。2.黄酮类化合物完全缓解kci诱导的强直收缩(IC50:染料木素20.2±2.0 μM, n = 11;山奈酚10.1±1.6 μM, n = 8;3在KCI前用10 μM和100 μM的rp - camp孵育30 min,使黄酮类化合物的剂量-响应曲线向右平移,染料木素的IC50分别达到27.8±3.8 μM和31.9±7.3 μM;山奈酚为24.7±0.2 μM, 19.6±4.9 μM;槲皮素含量分别为18.8±2.2 μM和18.4±1.5 μM。4 . Papaverine (3 ~ 100 μM)对KCI诱导的收缩也有缓解作用,且该作用与Rp-cAMPS (10 μM)显著右移(IC50为12.1±2.2 vs. 16.5±3.1 μM)。在收缩剂作用前15 min加入罂粟碱(3 μM)可使黄酮类化合物的松弛作用增强,IC50显著降低(染料木素20.2±2.0 vs 9.8±1.4 μM;山奈酚10.1±1.6 vs. 6.6±0.7 μM;槲皮素13.2±1.2 vs. 7.8±1.4 μM)。5阿替洛尔(10 μM)不改变黄酮类化合物的松弛作用。在相同的实验条件下,普萘洛尔(10 μM)对染料木素和山奈酚的作用没有影响,但对槲皮素的响应曲线有显著的右移(13.2±1.2 vs. 17.7±3.4 μM)。6结果提示染料木素、山奈酚和槲皮素通过增加细胞内cAMP使子宫平滑肌松弛。β-肾上腺素受体也可能参与槲皮素的作用。
Involvement of cAMP and β-adrenoceptors in the relaxing effect elicited by flavonoids on rat uterine smooth muscle
1 The effect of the flavonoids genistein (3–100 μM), kaempferol (3–60 μM) and quercetin (1–100 μM) on KCI (60 mM)-induced tonic contraction in rat smooth muscle was assayed. In the same way, the modification of these effects in the presence of an inhibitor of protein kinase (PKA) (Rp-cAMPS), an inhibitor of phosphodiesterase (papaverine) and β-adrenoreceptor blocking agents (propranolol and atenolol) was studied.
2 The flavonoids totally relaxed the KCI-induced tonic contraction (IC50: genistein 20.2 ± 2.0 μM, n = 11; kaempferol 10.1 ± 1.6 μM, n = 8; quercetin 13.2 ± 1.2 μM, n = 8).
3 The incubation with Rp-cAMPS (10 and 100 μM) 30 min prior to KCI shifted the dose-response curve of the flavonoids to the right, increasing their IC50 up to 27.8 ± 3.8 and 31.9 ± 7.3 μM, respectively, for genistein; 24.7 ± 0.2 and 19.6 ± 4.9 μM, respectively, for kaempferol; 18.8 ± 2.2 and 18.4 ± 1.5 μM, respectively, for quercetin.
4 Papaverine (3–100 μM) also relaxed the contraction induced by KCI and this effect was significantly displaced to the right with Rp-cAMPS (10 μM) (IC50 12.1 ± 2.2 vs. 16.5 ± 3.1 μM). Papaverine (3 μM) added to the organ bath 15 min before the contractile agent increased the relaxing effect of the flavonoids and significantly decreased their IC50 (genistein 20.2 ± 2.0 vs. 9.8 ± 1.4 μM; kaempferol 10.1 ± 1.6 vs. 6.6 ± 0.7 μM; quercetin 13.2 ± 1.2 vs. 7.8 ± 1.4 μM).
5 The incubation with atenolol (10 μM) did not alter the relaxing effect of the flavonoids. In the same experimental conditions, propranolol (10 μM) did not modify the effect of genistein and kaempferol, but shifted the response curve of quercetin significantly to the right (13.2 ± 1.2 vs. 17.7 ± 3.4 μM).
6 The results suggest that genistein, kaempferol and quercetin produced the relaxation of uterine smooth muscle by increasing intracellular cAMP. β-Adrenoceptors could also be involved in the effect of quercetin.