The hypothalamic endocannabinoid system participates in the secretion of oxytocin and tumor necrosis factor-alpha induced by lipopolysaccharide.
This study investigated the participation of the hypothalamic endocannabinoid system in the response to lipopolysaccharide (LPS) challenge evaluating oxytocin (OXT) and tumor necrosis factor-alpha (TNF-alpha) plasma levels in vivo and their release from hypothalamic fragments in vitro. LPS increased OXT and TNF-alpha release through anandamide-activation of hypothalamic cannabinoid receptor CB(1,) since the antagonist AM251 blocked this effect. Anandamide, through its receptors, also increased hypothalamic nitric oxide (NO) which inhibited OXT release, ending the stimulatory effect of the endocannabinoid. Our findings reveal a hypothalamic interaction between oxytocin, endocannabinoid and NO-ergic systems providing a regulation of the hypothalamic-neurohypophyseal axis under basal and stress conditions.
De Laurentiis
Andrea
A
Centro de Estudios Farmacológicos y Botánicos, CEFYBO-CONICET-UBA, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina. andredelaurentiis@yahoo.com
Fernandez-Solari
Javier
J
Mohn
Claudia
C
Burdet
Berenice
B
Zorrilla Zubilete
María A
MA
Rettori
Valeria
V
D000704:Analysis of Variance; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D063385:Cannabinoid Receptor Modulators / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D002219:Carbamates / Q000494:pharmacology; D063388:Endocannabinoids; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D010121:Oxytocin / Q000097:blood*; D053284:Polyunsaturated Alkamides / Q000494:pharmacology; D011863:Radioimmunoassay / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
D001095:Arachidonic Acids; D001549:Benzamides; D063385:Cannabinoid Receptor Modulators; D002219:Carbamates; D063388:Endocannabinoids; D007211:Indoles; D008070:Lipopolysaccharides; D053284:Polyunsaturated Alkamides; D043884:Receptor, Cannabinoid, CB1; D014409:Tumor Necrosis Factor-alpha; C500528:cyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl ester; D009569:Nitric Oxide; D010121:Oxytocin; C094023:iodopravadoline; C078814:anandamide