Inhibitory effects of indicaxanthin on mouse ileal contractility: analysis of the mechanism of action.

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.