| Enhancement of the hypotensive effects of intrathecally injected endocannabinoids by the entourage compound palmitoylethanolamide. | |
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MedLine Citation:
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PMID: 19289116 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The intrathecal (i.t.) injection of 50 and 100 nmol anandamide to urethane anesthetized rats induced a dose-dependent decrease in the mean blood pressure (-10.6+/-1.6 mmHg and -15.0+/-1.7 mmHg, respectively; n=6) whereas a lower dose of this endocannabinoid (25 nmol) was devoid of effect. Similar responses were obtained both with the non-metabolizable analog methanandamide and with the endocannabinoid N-arachidonoyldopamine. When the sub-effective dose (25 nmol) of each compound was co-injected with palmitoylethanolamide (100 nmol), significant decreases in the blood pressure were observed (-12.3+1.3 mmHg for anandamide; -12.1+/-0.8 mmHg for methanandamide; -12.1+/-0.8 mmHg for N-arachidonoyldopamine; n=4-6). Palmitoylethanolamide also enhanced the hypotensive responses to the 50 nmol-dose of both anandamide and methanandamide. The hypotensive response induced by co-administration of palmitoylethanolamide and 25 nmol anandamide was prevented both by the cannabinoid CB(1) receptor antagonist SR 144716A (20 nmol; i.t.) and by the vanilloid TRPV1 receptor antagonist capsazepine (20 nmol; i.t.) and enhanced by pretreatment with URB602 (3.5 nmol; i.t.), a putative inhibitor of palmitoylethanolamide degradation. These results suggest that in the spinal cord palmitoylethanolamide acts as an entourage compound for the hypotensive effects of i.t. administered endocannabinoids. The facilitative action of palmitoylethanolamide affects the vanilloid TRPV1 as well as the cannabinoid CB(1) receptor-mediated effects of endocannabinoids on the blood pressure control. |
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Authors:
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María del Carmen García; Edda Adler-Graschinsky; Stella Maris Celuch |
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Publication Detail:
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Type: Journal Article Date: 2009-03-14 |
Journal Detail:
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Title: European journal of pharmacology Volume: 610 ISSN: 1879-0712 ISO Abbreviation: Eur. J. Pharmacol. Publication Date: 2009 May |
Date Detail:
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Created Date: 2009-04-28 Completed Date: 2009-07-29 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 1254354 Medline TA: Eur J Pharmacol Country: Netherlands |
Other Details:
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Languages: eng Pagination: 75-80 Citation Subset: IM |
Affiliation:
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Cátedra de Farmacología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, 5 degrees piso, 1113 Buenos Aires, Argentina. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antihypertensive Agents / pharmacology* Biphenyl Compounds / pharmacology Blood Pressure / drug effects* Capsaicin / analogs & derivatives, pharmacology Dose-Response Relationship, Drug Drug Synergism Endocannabinoids / administration & dosage, pharmacology* Heart Rate / drug effects Injections, Spinal Male Palmitic Acids / antagonists & inhibitors, pharmacology* Rats Rats, Sprague-Dawley Receptors, Cannabinoid / antagonists & inhibitors TRPV Cation Channels / antagonists & inhibitors |
| Chemical | |
Reg. No./Substance:
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0/Antihypertensive Agents; 0/Biphenyl Compounds; 0/Endocannabinoids; 0/Palmitic Acids; 0/Receptors, Cannabinoid; 0/TRPV Cation Channels; 0/Trpv1 protein, rat; 0/URB602; 0/capsazepine; 404-86-4/Capsaicin; 544-31-0/palmidrol |
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