CEFYBO   02669
CENTRO DE ESTUDIOS FARMACOLOGICOS Y BOTANICOS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Participation of the endocannabinoid system in the effect of TNF-alpha to decrease hypothalamic cAMP content
Autor/es:
JAVIER FERNANDEZ SOLARI; JUAN PABLO PRESTIFILIPPO; ANDREA DE LAURENTIIS; CLAUDIA MOHN; SILVIA BILLI; ANA FRANCHI; SAMUEL MCCANN; VALERIA RETTORI
Lugar:
Clearwater, Florida, USA
Reunión:
Congreso; XV Symposium on the Cannabinoids; 2006
Institución organizadora:
International Cannabinoids Research Society
Resumen:
La fecha de publicación es 2005 pero ha sido modificada para que el sistema lo considere dentro del período informado que abarca desde julio de 2005 hasta diciembre de 2006 por ser mi primer informe de Investigador Asistente. It is well known that cannabinoids alter many reproductive parameters in animals and humans. Our group reported previously that delta-9-tetrahydrocannabinol (THC) injected into the third cerebral ventricle (icv) reduced plasma luteinizing hormone (LH) levels, and in vitro studies indicated that this suppressive effect was mediated by a blockade of LH releasing hormone (LHRH) release. More recent studies indicated that the endocannabinoid anandamide (AEA) injected icv decreased plasma LH. Also, we reported previously that AEA decreased cAMP content in medial basal hypothalamus (MBH) incubated in vitro inducing a decrease in LHRH release. On the other hand, we have shown previously that the intraperitoneal (ip) administration of lipopolysaccharide (LPS) decreases plasma LH as well as icv injection of TNF-alpha. Since endocannabinoids have been shown to affect a variety of immune cell functions, we hypothesized that TNF-alpha could decrease LHRH release by increasing AEA in the hypothalamus. It was reported that LPS down regulates fatty acid amide hydrolase (FAAH) expression and therefore increases AEA plasma levels. The present studies show that an acute ip injection of LPS to male Wistar adult rats significantly (p<0.05) increased hypothalamic AEA synthesis after 3 hs. It is well known that the activation of CB receptors (CB-r) negatively regulates adenylyl cyclase (AC) activity. The present experiments demonstrated that the incubation of MBH in the presence of forskolin (an activator of AC) increased highly significantly (p<0.001) cAMP that was almost completely abolished (p<0.001) by the presence of TNF-alpha. Moreover this effect of TNF-alpha was significantly (p<0.05) but not completely blocked by the addition of AM251 (a CB1-r antagonist) indicating that it is mediated at least in part by endocannabinoids. In summary, these results showed that AEA may play a pathophysiological role in mediating the action of proinflamatory cytokines, such as TNF alpha by decreasing cAMP, resulting in decreased LHRH followed by decreased LH release. (Supported by BID 1201 OC-AR PICT 14264-03)