We aimed to prospectively examine β-adrenoceptor-mediated uterine contractility in women suffering from gynecological malignancies. Myometrial specimens were obtained from non-pregnant women undergoing hysterectomy for benign gynecological disorders, and ovarian, endometrial, synchronous ovarian–endometrial, and cervical cancer. Contractions of myometrial strips in an organ bath before and after cumulative dosages of β2- and β3-adrenoceptor agonists with preincubation of propranolol, SR 59230A, and butoxamine were studied. All agonists induced a dose-dependent attenuation for uterine contractility in endometrial or cervical cancer, similar to that observed in the reference group. Contradictory effects were observed for ovarian cancer alone or in combination with endometrial cancer. CL 316243 or ritodrine abolished the relaxation, whereas BRL 37344 increased the uterine contractility in ovarian cancer. Moreover, β-adrenoceptor antagonists caused varied effects for β2- or β3-adrenoceptor agonists. Our experiments demonstrate that ovarian cancer, alone or as synchronous ovarian–endometrial cancer, substantially alters uterine contractility in response to β-adrenoceptor agonists.Electronic supplementary materialThe online version of this article (doi:10.1007/s12576-016-0500-1) contains supplementary material, which is available to authorized users.
There is now considerable evidence for the involvement of K+ channels in nitric oxide (NO) induced relaxation of smooth muscles including the myometrium. In order to assess whether apamin-sensitive K+ channels play a role in NO – induced relaxation of the human uterus, we have studied the effect of specific blockers of these channels on the relaxation of myometrium from non-pregnant women. In vitro isometric contractions were recorded in uterine tissues from non-pregnant premenopausal women who had undergone hysterectomy. Apamin (10 nM) and scyllatoxin (10 nM) did not alter spontaneous myometrial contractions. However, 15-min pretreatment of the myometrium strips with apamin completely inhibited relaxation caused by diethylamine-nitric oxide (DEA/NO). The pretreatment with scyllatoxin significantly reduced (about 2.6 times) maximum relaxation of the strips induced by DEA/NO (p < 0.05). These results strongly suggest that, beside Ca2+ and voltage dependent charybdotoxin-sensitive (CTX-sensitive) K+ channels, apamin-sensitive K+ channels are also present in the human non-pregnant myometrium. These channels offer an additional target in the development of new tocolytic agents.
Background: Quercetin has recently become a remarkably popular subject of research due to its broad beneficial pharmacological properties. The goal of our study was to observe its effects on contractility of human gastric smooth muscles in reference to the NO pathway and direct influence of potassium channels.Methods: Tissues were obtained from patients undergoing sleeve gastrectomy due to morbid obesity (n = 10 aged 24-56; BMI 47.16 ± 1.84). The following parameters were evaluated in the recordings: area under the curve (AUC), average baseline muscle tone, and relative change in muscle contraction. Key Results: Quercetin induced noticeable, dose-dependent relaxation of the carbachol treated gastric strips. The substantial effect was noted at concentrations higher than 10 −7 mol/L and maximal at 10 −4 mol/L (81.82 ± 3.32%; n = 10; p < 0.0001) of the control.Neither NOS blockers nor guanylyl cyclase blockers had inhibitory effects on the relaxation of strips induced by examined polyphenol. Glibenclamide inhibited the relaxing effect of quercetin, significant at concentrations higher than 5⋅10 −5 mol/L. Preincubation with charybdotoxin or apamin extended the relaxing effect of quercetin (from 10 −6 mol/L).Tamoxifen, in turn, significantly increased muscle relaxation at all quercetin concentrations.
Conclusions & Inferences:In conclusion, the current study was the first to show that quercetin-induced relaxation of human gastric smooth muscle occurs directly through K + ATP channels and independently to NO pathways. The present results suggest that quercetin is a potential nutraceutical in the treatment of functional gastrointestinal dyspepsia and other minor gastric muscle motility disturbance.
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