title: Role of the endocannabinoid system in the control of mouse myometrium contractility during the menstrual cycle.
abstract: Cannabis and cannabinoids are known to affect female reproduction. However, the role of the endocannabinoid system in mouse uterine contractility in the dioestrus and oestrus phases has not been previously investigated. The present study aimed at filling this gap. Endocannabinoid (anandamide and 2-arachidonoylglycerol) levels were measured in mouse uterus at dioestrus and oestrus phases by liquid chromatography-mass spectrometry; quantitative reverse transcription-PCR and western blot were used to measured the expression of cannabinoid receptors and enzymes involved in the metabolism of endocannabinoids. Contractility was evaluated in vitro either on the spontaneous contractions or by stimulating the isolated uterus with exogenous spasmogens. The tissue concentrations of anandamide and 2-AG were reduced in the oestrus phase, compared to dioestrus. Uteri obtained in the dioestrus, but not oestrus, phase showed spontaneous phasic prostaglandin-mediated contractions that were reduced by ACEA (CB1receptor agonist) and to a lower extent by JWH133 (CB2receptor agonist). These inhibitory effects were counteracted by the corresponding selective antagonists. Neither ACEA nor JWH133 did affect the contractions induced by exogenous PGE2in the uterus from the oestrus phase. The FAAH inhibitor JNJ1661010 and, to a lower extent, the MAGL inhibitor JZL184 also reduced spontaneous contractions. It is concluded that the endocannabinoid system undergoes to adaptive changes between the oestrus and dioestrus phases. CB1and, to a lower extent, CB2receptor activation results in selective inhibition of myometrial contractility, without un-specific relaxing effects on the smooth muscle. These results might be of interest for female marijuana smokers as well as for the design of novel tocolytic agents.
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Naples, Italy; Endocannabinoid Research Group, National Research Council, Naples, Italy.
authors.forename: Ester
authors.initials: E
authors.lastname: Pagano
authors.affiliation: Endocannabinoid Research Group, National Research Council, Naples, Italy; Institute of Protein Biochemistry, National Research Council, Naples, Italy; Institute of Applied Sciences & Intelligent Systems, National Research Council, Pozzuoli, Naples, Italy.
authors.forename: Pierangelo
authors.initials: P
authors.lastname: Orlando
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Naples, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Finizio
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Naples, Italy.
authors.forename: Antonietta
authors.initials: A
authors.lastname: Rossi
authors.affiliation: Endocannabinoid Research Group, National Research Council, Naples, Italy; Institute of Biomolecular Chemistry, National Research Council, Pozzuoli, Naples, Italy.
authors.forename: Lorena
authors.initials: L
authors.lastname: Buono
authors.affiliation: Endocannabinoid Research Group, National Research Council, Naples, Italy; Institute of Biomolecular Chemistry, National Research Council, Pozzuoli, Naples, Italy.
authors.forename: Fabio Arturo
authors.initials: FA
authors.lastname: Iannotti
authors.affiliation: Endocannabinoid Research Group, National Research Council, Naples, Italy; Institute of Biomolecular Chemistry, National Research Council, Pozzuoli, Naples, Italy.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Piscitelli
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Naples, Italy; Endocannabinoid Research Group, National Research Council, Naples, Italy.
authors.forename: Angelo A
authors.initials: AA
authors.lastname: Izzo
authors.affiliation: Endocannabinoid Research Group, National Research Council, Naples, Italy; Institute of Biomolecular Chemistry, National Research Council, Pozzuoli, Naples, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Marzo
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Naples, Italy; Endocannabinoid Research Group, National Research Council, Naples, Italy. Electronic address: franborr@unina.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: Borrelli
mesh_terms: D000818:Animals; D063388:Endocannabinoids / Q000502:physiology*; D030762:Estrous Cycle; D005260:Female; D051379:Mice; D008813:Mice, Inbred ICR; D012333:RNA, Messenger / Q000378:metabolism; D014590:Uterine Contraction / Q000502:physiology*
chemical_list: D063388:Endocannabinoids; D012333:RNA, Messenger
keywords: Cannabis; Endogenous cannabinoid system; Menstrual cycle; Myometrium contractility; Tocolysis