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| Content Provider | PubMed Central |
|---|---|
| Author | Javier, Fernández-solari Scorticati, Camila Mohn, Claudia De Laurentiis, Andrea Billi, Silvia Franchi, Ana Mccann, Samuel M. Valeria, Rettori |
| Copyright Year | 2004 |
| Abstract | We hypothesized that ethanol (EtOH) might act through the endocannabinoid system to inhibit luteinizing hormone-releasing hormone (LHRH) release. Therefore, we examined the mechanism by which EtOH and anandamide (AEA), an endogenous cannabinoid, inhibit LHRH release from incubated medial basal hypothalamic explants. In previous work, we demonstrated that EtOH inhibits the N-methyl-d-aspartic acid-stimulated release of LHRH by increasing the release of two neurotransmitters: β-endorphin and γ-aminobutyric acid (GABA). In the present work, bicuculline, a GABAergic antagonist, completely prevented the inhibition of AEA (10-9M) on N-methyl-d-aspartic acid-induced LHRH release, but naltrexone, a μ-opioid receptor antagonist, had no effect. AEA also significantly increased GABA release but had no effect on β-endorphin release. Therefore, AEA could inhibit LHRH release by increasing GABA but not β-endorphin release. Because EtOH and AEA acted similarly to inhibit LHRH release, we investigated whether both substances would affect the adenylate cyclase activity acting through the same GTP-coupled receptors, the cannabinoid receptors 1 (CB1-rs). AEA and EtOH (10-1M) reduced the forskolin-stimulated accumulation of cAMP, but AM251, a specific antagonist of CB1-r, significantly blocked that inhibition. Additionally we investigated whether CB1-r is involved in the inhibition of LHRH by EtOH and AEA. AEA and EtOH reduced forskolin-stimulated LHRH release, but AM251 significantly blocked that inhibition. Also, we demonstrated that EtOH did not act by increasing AEA synthase activity to inhibit LHRH release in our experimental conditions. Therefore, our results indicate that EtOH inhibits the release of LHRH acting through the endocannabinoid system. |
| Related Links | http://dx.doi.org/10.1073/pnas.0307346101 |
| Ending Page | 3268 |
| Page Count | 5 |
| Starting Page | 3264 |
| File Format | |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 9 |
| Volume Number | 101 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2004-03-02 |
| Access Restriction | Open |
| Rights Holder | National Academy of Sciences |
| Subject Keyword | General Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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