Dennedy Michael C, Friel Ann M, Houlihan Diarmaid D, Broderick Venita M, Smith Terry, Morrison John J
Department of Obstetrics and Gynecology, Clinical Sciences Institute, National University of Ireland, Galway, Ireland.
Am J Obstet Gynecol. 2004 Jan;190(1):2-9; discussion 3A. doi: 10.1016/j.ajog.2003.07.013.
The aim of this study was to investigate the expression of cannabinoid receptors in human uterine smooth muscle during pregnancy and to evaluate the effects of endogenous and exogenous cannabinoids on myometrial contractility in vitro.
Human myometrial biopsy specimens were obtained at elective cesarean delivery and snap frozen or mounted for isometric recording under physiologic conditions. Cumulative doses of the endogenous cannabinoid anandamide or the exogenous cannabinoid Delta(9) (indicates a double bond between carbons 9 and 10) tetrahydrocannabinol were added in the range 1 nmol/L to 100 micromol/L. Selectivity of the cannabinoid receptor agonists was investigated with specific antagonists for the CB(1) and the CB(2) receptors. Reverse transcription-polymerase chain reaction with primers for the CB(1) and CB(2) receptors was performed on messenger RNA that was isolated from human pregnant myometrium.
Both anandamide and Delta(9)-tetrahydrocannabinol exerted a direct relaxant effect on human pregnant myometrium in vitro, which was of equal potency for both compounds. This relaxant effect was antagonized by the specific CB(1) receptor antagonist, SR 141716, but not by the specific CB(2) receptor antagonist, SR 144528 (n=6 specimens, P<.01). Both the CB(1) and CB(2) receptors are expressed in human myometrium.
Both endogenous and exogenous cannabinoids exert a potent and direct relaxant effect on human pregnant myometrium, which is mediated through the CB(1) receptor. This highlights a possible role for endogenous cannabinoids during human parturition and pregnancy. These results also support the view that the use of exogenous cannabinoids during pregnancy is not linked independently with preterm labor.
本研究旨在调查妊娠期间人子宫平滑肌中大麻素受体的表达，并评估内源性和外源性大麻素对体外子宫肌层收缩性的影响。
在择期剖宫产时获取人子宫肌层活检标本，速冻或在生理条件下固定以进行等长记录。加入1 nmol/L至100 μmol/L范围内的内源性大麻素花生四烯乙醇胺或外源性大麻素Δ⁹（表示碳9和碳10之间的双键）四氢大麻酚的累积剂量。用CB₁和CB₂受体的特异性拮抗剂研究大麻素受体激动剂的选择性。对从人妊娠子宫肌层分离的信使核糖核酸进行CB₁和CB₂受体引物的逆转录-聚合酶链反应。
花生四烯乙醇胺和Δ⁹-四氢大麻酚在体外均对人妊娠子宫肌层产生直接舒张作用，两种化合物的效力相当。这种舒张作用被特异性CB₁受体拮抗剂SR 141716拮抗，但未被特异性CB₂受体拮抗剂SR 144528拮抗（n = 6个标本，P <.01）。CB₁和CB₂受体均在人子宫肌层中表达。
内源性和外源性大麻素均对人妊娠子宫肌层产生强大的直接舒张作用，这是通过CB₁受体介导的。这突出了内源性大麻素在人类分娩和妊娠期间可能发挥的作用。这些结果也支持了妊娠期间使用外源性大麻素与早产无独立关联的观点。
