Effects of endocannabinoids on the isolated rabbit myometrium: An experimental invitro study

Headnote

Keywords: Cannabinoid receptors, electrical field stimulation, endocannabinoids, rabbit myometrium

[OP-209]

Objective: It was shown that cannabinoids act on uterine smooth muscle "myometrium" contractility. However, the role and effect of the endocannabinoid system in myometrial function are still controversial. The aim of this study is to evaluate the effects of endocannabinoids on myometrial contractility and to investigate through which cannabinoid receptors these effects are created in isolated rabbit myometrium.

Material and Methods: Myometrial strips (3x15 mm longitudinal) obtained from albino female rabbits (2.5-3 kg adult rabbits; n=20) were mounted in organ baths containing modified Krebs solution and were tested for changes in isometric tension. Electrical field stimulation (EFS) parameters were selected as 60 V with 1 ms duration in 10-s trains at 8-16 Hz frequencies at 2-min intervals to obtain isometric contractions. Then, anandamide (endogenous cannabinoid agonist; 10-7 - 3x10-5 M; n=7), WIN 55,212-2 (cannabinoid receptor agonist; 10-8 - 3x10-5 M; n=6), ACEA (selective CB1 agonist; 10-7 - 3x10-5 M; n=7), JWH015 (selective CB2 agonist; 10-8 - 3x10-5 M; n=6) were separately administered on EFS-mediated myometrial contractions. Additionally, the drugs mentioned above were evaluated on EFS-mediated contractions in the presence of indomethacin (10-5 M; n=7, n=4, n=4, n=4). To explore the contributions of the receptors, the effects of these drugs were appraised in the presence of AM 251 (CB1 receptor antagonist; 10-6 M; n=5, n=5, n=4), and AM 630 (CB2 receptor antagonist; 10-6 M; n=5, n=5, n=7). The direct effects of these drugs on myometrial smooth muscle were conducted in carbachol (cholinergic agonist)-induced contracted myometrial strips.

Results: Anandamide, WIN 55,212-2, ACEA and JWH015 produced a concentration-dependent reduction on EFS-evoked contrac - tions (p<0.05). The inhibitor effects of anandamide, WIN 55,212-2, JWHO15 and ACEA did not change in the presence of AM 251 and AM 630 in separately and together as well (p>0.05). The inhibitor effects of anandamide and WIN 55,212-2 increased significantly in the presence of indomethacin (p<0.05). There were no relaxant effects of all these drugs on the tissues contracted with carbachol (p>0.05).

Conclusion: Endocannabinoids exerted an inhibitory effect on EFSevoked myometrial isometric contractions and they probably exhibited this effect via presynaptic interaction. This inhibitory effect of endocannabinoids suggests it may play a physiologic role in regulation of myometrial activity and further studies to evaluate the signaling pathways involved may help to define this role.