CONICET | Buscador de Institutos y Recursos Humanos

Objective: The aim of the present paper was to study whether lipopolysaccharide (LPS) induced-inhibition of salivary secretion involves the activation of the endocannabinoid system and the participation of tumor necrosis factor (TNF)á in the submandibular gland. Design: Pharmacological approaches were performed by using CB1 and/or CB2 cannabinoid receptor antagonists, AM251 and AM630, respectively, injected into the submandibular gland, to study the participation of the endocannabinoid system in LPS inhibitory effects on metacholine- induced salivary secretion. Anandamide synthase activity was measured after LPS injection as indicator of endocannabinoid system activation. To study the participation of TNFá on LPS inhibitory effects, salivary secretion was studied after LPS intraperitoneal injection with the blockade on TNFá action by a soluble form of TNF receptor, etanercept. Finally, to link TNFá and endocannabinoids participation on submandibular gland reduced function during LPS challenge, this cytokine was injected intraglandularly alone or concomitantly with AM251 and AM630 to evaluate their effects on salivary secretion. Results: AM251 and AM630 partially prevented LPS induced inhibition of salivation when were injected separately or concomitantly. Also, anandamide synthase activity in submandibular gland was increased after LPS injection. On the other hand, etanercept, prevented the inhibitory effect of LPS on salivary secretion and moreover, TNFá injected intraglandularly inhibited salivary secretion, been this effect prevented by AM251 and AM630 injected concomitantly. Conclusion: the present results demonstrate the participation of the endocannabinoid system and TNFá on salivary responses during systemic inflammation induced by LPS.