title: Effects of d- and l-limonene on the pregnant rat myometrium in vitro.
abstract: OBJECTIVE
  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 l-limonene (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.
  
  
  CONCLUSIONS
  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 Ca(2+) channel. It is possible that limonene-containing products increase the pregnant uterus contractility and their use should be avoided during pregnancy.
authors.forename: Judit
authors.initials: J
authors.lastname: Hajagos-Tóth
authors.forename: Ágnes
authors.initials: Á
authors.lastname: Hódi
authors.forename: Adrienn B
authors.initials: AB
authors.lastname: Seres
authors.affiliation: Róbert Gáspár, Szeged, H-6701, P.O. Box 121, Hungary, gaspar@pharm.u-szeged.hu.
authors.forename: Róbert
authors.initials: R
authors.lastname: Gáspár
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D053138:Cyclohexenes / Q000494:pharmacology*; D005260:Female; D007211:Indoles / Q000494:pharmacology; D000077222:Limonene; D008297:Male; D009215:Myometrium / Q000187:drug effects* / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D043705:Receptor, Adenosine A2A / Q000378:metabolism; D013729:Terpenes / Q000494:pharmacology*; D019789:Tetraethylammonium / Q000494:pharmacology; D013806:Theophylline / Q000494:pharmacology; D014590:Uterine Contraction / Q000187:drug effects*
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D053138:Cyclohexenes; D007211:Indoles; D026902:Potassium Channel Blockers; D043705:Receptor, Adenosine A2A; D013729:Terpenes; C048220:paxilline; D019789:Tetraethylammonium; D000077222:Limonene; D013806:Theophylline; D000242:Cyclic AMP; D009543:Nifedipine; D009638:Norepinephrine