Aim: To study the effects of d- and l-limonene on pregnant rat myometrial contractility in vitro, and investigate how these effects are modified by other agents. D- and llimonene (10-13-10-8 M) caused myometrial contraction in a dose-dependent manner. Methods: Contractions of uterine rings from 22-day-pregnant rats were measured in an organ bath in the presence of d- or l-limonene (10-13-10-8 M) and nifedipine (10-8 M), tetraethyl-ammonium (10-3 M), theophylline (10-5 M), or paxilline (10-5 M). Uterine cyclic adenosine monophosphate (cAMP) level was detected by enzyme immunoassay. Oxidative damage was induced by methylglyoxal (3× 10-2 M) and the alteration was measured via noradrenaline (1× 10-9 to 3× 10-5 M) -induced contractions. Results: Pre-treatment with nifedipine (10-8 M), tetraethylammonium (10-3 M), and theophylline (10-5 M) attenuated the contracting effect of d- and l-limonene, while in the presence of paxilline (10-5 M) d- and l-limonene were ineffective. The two enantiomers decreased the myometrial cAMP level, but after paxilline pretreatment the cAMP level was not altered compared with the control value. Additionally, l-limonene (10-6 M) diminished consequences of oxidative damage caused by methylglyoxal (3× 10-2 M) on contractility, whereas d-limonene was ineffective. Conclusion: Our findings suggest that l-limonene has an antioxidant effect and that both d-and l-limonene cause myometrial contraction through activation of the A2A receptor and opening of the voltage-gated Ca2+ channel. It is possible that limonene-containing products increase the pregnant uterus contractility and their use should be avoided during pregnancy.
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