Effects of abnormal cannabidiol on oxytocin-induced myometrial contractility.
The objective of this study was to investigate the effects of abnormal cannabidiol (abn-cbd) on oxytocin-induced myometrial contractility occurring during pregnancy. Isometric tension recordings were performed in isolated myometrial strips from biopsies obtained at elective cesarean section. The effects of cumulative doses of abn-cbd (10(-9)-10(-5) M) on oxytocin-induced myometrial contractions alone, and on those following pre-incubation with SR 144528, AM 251, methylene blue, and iberiotoxin were measured, and dose-response curves were constructed. The pD(2) (-log EC(50)) values and the maximal inhibitory (MMI) values that were achieved were compared for each tissue type. Abn-cbd exerted a potent relaxant effect on oxytocin-induced myometrial contractions in vitro. Pre-incubation with the guanylate cyclase inhibitor, methylene blue, and the BK(Ca) channel antagonist, iberiotoxin, significantly attenuated this effect (for pD(2), P<0.01; for MMI, P<0.01). Abn-cbd exerts a potent inhibitory effect on human uterine contractility. This effect is partially mediated through modulation of guanylate cyclase and activation of BK(Ca) channel activity. These findings have implications for physiologic regulation of myometrial quiescence.
Houlihan
Diarmaid D
DD
Department of Obstetrics and Gynecology, Clinical Sciences Institute, University College Hospital, National University of Ireland Galway, Newcastle Road, Galway, Ireland.
Dennedy
Michael C
MC
Morrison
John J
JJ
D000328:Adult; D001892:Camphanes; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D007537:Isometric Contraction / Q000187:drug effects; D008875:Middle Aged; D009924:Organ Culture Techniques; D010121:Oxytocin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011247:Pregnancy; D011720:Pyrazoles; D043885:Receptor, Cannabinoid, CB2 / Q000037:antagonists & inhibitors; D012118:Resorcinols / Q000494:pharmacology*; D014590:Uterine Contraction / Q000187:drug effects* / Q000502:physiology; D055815:Young Adult
C479832:4-(3-3,4-p-menthadien-(1,8)-yl)olivetol; D001892:Camphanes; D006727:Hormone Antagonists; D011720:Pyrazoles; D043885:Receptor, Cannabinoid, CB2; D012118:Resorcinols; C110630:SR 144528; D010121:Oxytocin