Lipopolysaccharide (LPS) activates the endocannabinoid system in the submandibulary gland of the rat

JUAN PABLO PRESTIFILIPPO; JAVIER FERNÁNDEZ SOLARI; JUAN CARLOS ELVERDIN; ANGELA SUBURO; SAMUEL M. MCCANN; VALERIA RETTORI

Tihany, Budapest (Hungary)

Congreso; XVI Symposium on the Cannabinoids; 2006

International cannabinoid Research Society

It was shown previously (Lomniczi et al Am J Physiol 281:405-411, 2001) that LPS inhibits saliva secretion by increasing PGE2 production. Also, it is well known that TNFa is rapidly released after LPS administration and mediates a number of the endotoxin functions. On the other hand, it is known that marihuana use decreases saliva secretion. Furthermore, we have previously demonstrated that type 1 and 2 cannabinoid receptors (CB-rs) are localized in the submandibulary gland (SMG) and their activation mediates the inhibition of salivation. On the basis of previous studies that showed an interaction between LPS responses and the endocannabinoid system, the aim of the present work was to investigate whether the endocannabinoid system could be activated during inflammation in the salivary glands of adult male Wistar rats. We found that anandamide (AEA) synthase activity measured by the radioconversion of 14C-arachidonic acid and ethanolamine to 14C-AEA was increased significantly (p<0.01) in SMG 3h after ip administration of LPS (5mg/Kg). Also, taking account that CB-rs are coupled to Gi proteins that respond by inhibiting adenylyl cyclase activity, we measured cAMP content 3h after LPS administration, and found that it was diminished significantly (p<0.05) in the SMG, which suggested CB-rs activation. Furthermore, we found that the in vitro incubation of SMGs slices in the presence of TNFa (2.9x10-9M) for 30 min markedly reduced (p<0.01) the forskolin-induced increase of cAMP content. This effect was blocked significantly (p<0.01) by AM251 (10-5M) but not by AM630 (10-5M) (CB1-r and CB2-r antagonists, respectively), indicating that CB1-r, but not CB2-r, are implicated in the TNFa activation of cannabinoid receptors in the SMG. In summary, the present results demonstrate that the endocannabinoid system is activated by proinflammatory signals in the submandibular glands. (Supported by PICT 03-14264)