| Cannabinoid ligand-receptor signaling in the mouse uterus. | |
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MedLine Citation:
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PMID: 7753807 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Using RNA (Northern) blot hybridization and reverse transcription-PCR, we demonstrate that the brain-type cannabinoid receptor (CB1-R) mRNA, but not the spleen-type cannabinoid receptor (CB2-R) mRNA, is expressed in the mouse uterus and that this organ has the capacity to synthesize the putative endogenous cannabinoid ligand, anandamide (arachidonylethanolamide). The psychoactive cannabinoid component of marijuana--delta 9-tetrahydrocannabinol (THC)--or anandamide, but not the inactive and nonpsychoactive cannabidiol (CBD), inhibited forskolin-stimulated cyclic AMP formation in the mouse uterus, which was prevented by pertussis toxin pretreatment. These results suggest that uterine CB1-R is coupled to inhibitory guanine nucleotide-binding protein and is biologically active. Autoradiographic studies identified ligand binding sites ([3H]anandamide) in the uterine epithelium and stromal cells, suggesting that these cells are perhaps the targets for cannabinoid action. Scatchard analysis of the binding of [3H]WIN 55212-2, another cannabinoid receptor ligand, showed a single class of high-affinity binding sites in the endometrium with an apparent Kd of 2.4 nM and Bmax of 5.4 x 10(9) molecules per mg of protein. The gene encoding lactoferrin is an estrogen-responsive gene in the mouse uterus that was rapidly and transiently up-regulated by THC, but not by CBD, in ovariectomized mice in the absence of ovarian steroids. This effect, unlike that of 17 beta-estradiol (E2), was not influenced by a pure antiestrogen, ICI 182780, suggesting that the THC-induced uterine lactoferrin gene expression does not involve estrogen receptors. We propose that the uterus is a new target for cannabinoid ligand-receptor signaling. |
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Authors:
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S K Das; B C Paria; I Chakraborty; S K Dey |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 92 ISSN: 0027-8424 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 1995 May |
Date Detail:
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Created Date: 1995-06-16 Completed Date: 1995-06-16 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 4332-6 Citation Subset: IM |
Affiliation:
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Department of Physiology, University of Kansas Medical Center, Ralph L. Smith Research Center, Kansas City 66160-7338, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Arachidonic Acids / metabolism, pharmacology Autoradiography Base Sequence Blotting, Northern Calcium Channel Blockers / pharmacology Cannabidiol / pharmacology Cannabinoids / pharmacology* Cannabis Cyclic AMP / metabolism DNA Primers Female Forskolin / pharmacology GTP-Binding Proteins / metabolism Gene Expression / drug effects Mice Mice, Inbred Strains Molecular Sequence Data Pertussis Toxin Polymerase Chain Reaction Polyunsaturated Alkamides Pregnancy RNA, Messenger / biosynthesis Receptors, Cannabinoid Receptors, Drug / biosynthesis, physiology* Signal Transduction* Tetrahydrocannabinol / pharmacology Tritium Uterus / drug effects, physiology* Virulence Factors, Bordetella / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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DA 06668/DA/NIDA NIH HHS; HD 12304/HD/NICHD NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Arachidonic Acids; 0/Calcium Channel Blockers; 0/Cannabinoids; 0/DNA Primers; 0/Polyunsaturated Alkamides; 0/RNA, Messenger; 0/Receptors, Cannabinoid; 0/Receptors, Drug; 0/Virulence Factors, Bordetella; 10028-17-8/Tritium; 13956-29-1/Cannabidiol; 1972-08-3/Tetrahydrocannabinol; 60-92-4/Cyclic AMP; 66428-89-5/Forskolin; 94421-68-8/anandamide; EC 2.4.2.31/Pertussis Toxin; EC 3.6.1.-/GTP-Binding Proteins |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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