Effects of abnormal cannabidiol on oxytocin-induced myometrial contractility

Houlihan, Diarmaid D.; Dennedy, Michael Conall

doi:10.1530/rep-09-0496

Cited by 6 publications

(3 citation statements)

References 29 publications

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“…There is evidence that PGE 2 , PGF 2␣ , and PGI 2 are up-regulated in the uterus and decidua at the onset of parturition (38), and enhance the contractile response/activity in the myometrium (39,40). Cyclooxygenases, Ptgs1 (Cox1) and Ptgs2 (Cox2) are two major enzymes that catalyze PG biosynthesis.…”

Section: Mice Exposed To Higher Endocannabinoid Signaling Are Susceptmentioning

confidence: 99%

Sustained Endocannabinoid Signaling Compromises Decidual Function and Promotes Inflammation-induced Preterm Birth

Sun

Deng

et al. 2016

Journal of Biological Chemistry

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Recent studies provide evidence that premature maternal decidual senescence resulting from heightened mTORC1 signaling is a cause of preterm birth (PTB). We show here that mice devoid of fatty acid amide hydrolase (FAAH) with elevated levels of N-arachidonyl ethanolamide (anandamide), a major endocannabinoid lipid mediator, were more susceptible to PTB upon lipopolysaccharide (LPS) challenge. Anandamide is degraded by FAAH and primarily works by activating two G-protein-coupled receptors CB1 and CB2, encoded by Cnr1 and Cnr2, respectively. We found that Faah ؊/؊ decidual cells progressively underwent premature senescence as marked by increased senescence-associated ␤-galactosidase (SA-␤-Gal) staining and ␥H2AX-positive decidual cells. Interestingly, increased endocannabinoid signaling activated MAPK p38, but not p42/44 or mTORC1 signaling, in Faah ؊/؊ deciduae, and inhibition of p38 halted premature decidual senescence. We further showed that treatment of a long-acting anandamide in wild-type mice at midgestation triggered premature decidual senescence utilizing CB1, since administration of a CB1 antagonist greatly reduced the rate of PTB in Faah ؊/؊ females exposed to LPS. These results provide evidence that endocannabinoid signaling is critical in regulating decidual senescence and parturition timing. This study identifies a previously unidentified pathway in decidual senescence, which is independent of mTORC1 signaling.

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Section: Mice Exposed To Higher Endocannabinoid Signaling Are Susceptmentioning

confidence: 99%

Sustained Endocannabinoid Signaling Compromises Decidual Function and Promotes Inflammation-induced Preterm Birth

Sun

Deng

et al. 2016

Journal of Biological Chemistry

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“…BK channel activation by cannabinoids was detected in myometrial strips (Houlihan et al, 2010), trabecular meshwork cells (Stumpff et al, 2005), ophthalmic artery (Romano and Lograno, 2006), coronary (White et al, 2001) and aortic SM (Sade et al, 2006), and HEK293 cells expressing BK α, α+β1 or α+β4 subunits (Sade et al, 2006; Godlewski et al, 2009). In contrast, μM methanandamide decreases BK activity in mesenteric and aortic SM (Bol et al, 2012).…”

Section: Cannabinoidsmentioning

confidence: 99%

“…Cannabinoid-induced BK activation seems to play a role in endothelium-dependent vasodilation (White et al, 2001; Romano and Lograno, 2006; Godlewski et al, 2009), modulation of ocular outflow (Stumpff et al, 2005), and myometrial quiescence (Houlihan et al, 2010). In addition, BK activation might contribute to cannabinoid-induced neuroprotection; in particular, to cannabidiol-induced protections against pentylenetetrazol-induced seizure (Shirazi-zand et al, 2013).…”

Section: Cannabinoidsmentioning

confidence: 99%

Lipid regulation of BK channel function

Dopico

Bukiya

2014

Front. Physiol.

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This mini-review focuses on lipid modulation of BK (MaxiK, BKCa) current by a direct interaction between lipid and the BK subunits and/or their immediate lipid environment. Direct lipid-BK protein interactions have been proposed for fatty and epoxyeicosatrienoic acids, phosphoinositides and cholesterol, evidence for such action being less clear for other lipids. BK α (slo1) subunits are sufficient to support current perturbation by fatty and epoxyeicosatrienoic acids, glycerophospholipids and cholesterol, while distinct BK β subunits seem necessary for current modulation by most steroids. Subunit domains or amino acids that participate in lipid action have been identified in a few cases: hslo1 Y318, cerebral artery smooth muscle (cbv1) R334,K335,K336, cbv1 seven cytosolic CRAC domains, slo1 STREX and β1 T169,L172,L173 for docosahexaenoic acid, PIP2, cholesterol, sulfatides, and cholane steroids, respectively. Whether these protein motifs directly bind lipids or rather transmit the energy of lipid binding to other areas and trigger protein conformation change remains unresolved. The impact of direct lipid-BK interaction on physiology is briefly discussed.

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