Altered uterine contractility in response to β-adrenoceptor agonists in ovarian cancer

Abstract

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.

G Protein-Coupled Receptors (GPCRs)-Mediated Calcium Signaling in Ovarian Cancer: Focus on GPCRs activated by Neurotransmitters and Inflammation-Associated Molecules

“…In a recent study, Modzelewska et al analyzed the alteration of β-adrenergic receptors in the mechanism of uterine contraction. β-adrenoceptor agonists (e.g., BRL 37344, CL 316243 or ritodrine) had a dose-dependent effect and diminished spontaneous myometrial contractions, in control, endometrial, and cervical cancer groups [49], while their cumulative administration failed to relax the myometrial strips from ovarian and synchronous ovarian–endometrial groups in opposition to the control group [49]. Additionally, administration of β-adrenoceptor antagonists (e.g., propranolol, SR 59230A, or butoxamine) was followed by varied effects on spontaneous uterine contractility when administered cumulatively with β2- or β3-adrenoceptor agonists, depending on the co-administered agonist or on the type of cancer in each examined group [49].…”

“…Taking into account that β2- or β3-adrenergic receptors have distinct functional alterations in ovarian, endometrial, and cervical cancer [49], pharmacological planning should consider these differences, as some patients are affected by many types of cancer. On the other hand, these functional differences should be further analyzed in terms of expression to assess to opportunity of using β-adrenergic receptors as histological markers.…”

Effects of Solvents, Emulsions, Cosolvents, and Complexions on Ex Vivo Mouse Myometrial Contractility

“…Early drug discovery, involving in vitro and ex vivo experiments, largely relies on aqueous-based assays. Ex vivo organ bath contractility assays using myometrial tissue remain an important screening tool for the discovery and development of effective, novel tocolytics and uterotonics [2,12,[20][21][22]. It is crucial for the investigational compound to be in a homogenous solution within the organ bath buffer for accurate determination of a compound's efficacy and potency.…”

β‐Adrenoceptors as drug targets in melanoma: novel preclinical evidence for a role of β3‐adrenoceptors

“…In addition, in humans, β 3 ‐adrenoceptors are overexpressed in colon and breast cancer (Perrone et al ., ; Montoya et al ., ), and a strong expression of β 3 ‐adrenoceptors has been found in infantile haemangiomas and vascular lesions (Chisholm et al ., ; Phillips et al ., ). There is also pharmacological evidence that β 3 ‐adrenoceptors are expressed in human ovarian and endometrial cancer (Modzelewska et al ., ). In addition, β 3 ‐adrenoceptor polymorphism has been associated with susceptibility to endometrial and breast cancer (Huang et al ., ; Babol et al ., ).…”