Dipartimento di Biologia cellulare e dello Sviluppo, Università di Palermo, 90128 Palermo, Italy.
Eur J Pharmacol. 2011 May 11;658(2-3):200-5. doi: 10.1016/j.ejphar.2011.02.034. Epub 2011 Mar 1.
Recently, we have showed that indicaxanthin, the yellow betalain pigment abundant in the fruit of Opuntia ficus indica, has remarkable spasmolytic effects on the intestinal contractility in vitro. Thus, the purpose of the present study was to investigate the mechanism of action underlying the observed response. We used organ bath technique to record the mechanical activity of the mouse ileum longitudinal muscle and ELISA to measure the levels of cAMP. Indicaxanthin induced inhibitory effects on spontaneous mechanical activity, which were unaffected by indomethacin, a non-selective inhibitor of cycloxygenase; 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, a selective inhibitor of nitric oxide-dependent guanylyl cyclase; 2'5'dideoxyadenosine, an adenylyl cyclase inhibitor; and zaprinast, a selective inhibitor of the cGMP phosphodiesterase isoenzyme. Indicaxanthin effects were reduced significantly in the presence of 3-isobutyl-1-methylxanthine (IBMX), a non selective inhibitor of phosphodiesterases (PDEs). Indicaxanthin and IBMX significantly reduced the carbachol-evoked contractions and the joint application of both drugs did not produce any additive effect. Indicaxanthin and IBMX increased the inhibitory effects of forskolin, an adenylyl cyclase activator, and the joint application of both drugs did not produce any additive effect. Indicaxanthin, contrarily to IBMX, did not affect the inhibitory action of sodium nitroprusside, a soluble guanylyl cyclase activator. Indicaxanthin increased both basal and forskolin-induced cAMP content of mouse ileal muscle. The present data show that indicaxanthin reduces the contractility of ileal longitudinal muscle by inhibition of PDEs and increase of cAMP concentration and raise the possibility of using indicaxanthin in the treatment of motility disorders, such as abdominal cramps.
最近，我们已经表明，在仙人掌果实中含量丰富的黄色甜菜红素——甜菜因，对离体肠道收缩性具有显著的松弛作用。因此，本研究的目的是探究观察到的反应的作用机制。我们使用器官浴技术记录小鼠回肠纵向肌的机械活动，并使用 ELISA 测量 cAMP 水平。甜菜因诱导自发性机械活动的抑制作用，不受非选择性环氧化酶抑制剂吲哚美辛的影响；1H-[1,2,4]恶二唑并[4,3-a]喹喔啉-1-酮，一种选择性抑制一氧化氮依赖的鸟苷酸环化酶的抑制剂；2'5'-双脱氧腺苷，一种腺苷酸环化酶抑制剂；以及扎普司特，一种 cGMP 磷酸二酯酶同工酶的选择性抑制剂。在存在 3-异丁基-1-甲基黄嘌呤（IBMX）时，甜菜因的作用显著降低，IBMX 是一种非选择性磷酸二酯酶（PDEs）抑制剂。甜菜因和 IBMX 显著降低了卡巴胆碱引起的收缩作用，联合应用两种药物没有产生任何相加作用。甜菜因和 IBMX 增加了腺苷酸环化酶激活剂福司可林的抑制作用，联合应用两种药物没有产生任何相加作用。与 IBMX 相反，甜菜因不影响可溶性鸟苷酸环化酶激活剂硝普钠的抑制作用。甜菜因增加了小鼠回肠的基础和福司可林诱导的 cAMP 含量。目前的数据表明，甜菜因通过抑制 PDEs 和增加 cAMP 浓度来降低回肠纵向肌的收缩性，并为使用甜菜因治疗运动障碍（如腹痛）提供了可能性。
