Cannabinoids and the human uterus during pregnancy.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Dennedy
Michael C
MC
Department of Obstetrics and Gynecology, Clinical Sciences Institute, National University of Ireland, Galway, Ireland.
Friel
Ann M
AM
Houlihan
Diarmaid D
DD
Broderick
Venita M
VM
Smith
Terry
T
Morrison
John J
JJ
D000328:Adult; D001095:Arachidonic Acids / Q000494:pharmacology*; D001892:Camphanes / Q000494:pharmacology; D013759:Dronabinol / Q000494:pharmacology*; D063388:Endocannabinoids; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D009215:Myometrium / Q000187:drug effects / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides; D011247:Pregnancy / Q000502:physiology*; D011720:Pyrazoles / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000235:genetics; D043885:Receptor, Cannabinoid, CB2 / Q000037:antagonists & inhibitors / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077285:Rimonabant; D014590:Uterine Contraction / Q000187:drug effects; D014599:Uterus / Q000187:drug effects*
D001095:Arachidonic Acids; D001892:Camphanes; D063388:Endocannabinoids; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles; D012333:RNA, Messenger; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; C110630:SR 144528; D013759:Dronabinol; D000077285:Rimonabant; C078814:anandamide