Participation of the endocannabinoid system in lipopolysaccharide-induced inhibition of salivary secretion.
OBJECTIVE
The aim of the present paper was to assess whether lipopolysaccharide (LPS)-induced inhibition of salivary secretion involves the activation of the endocannabinoid system and the participation of tumor necrosis factor (TNF)alpha in the submandibular gland.


METHODS
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. To assess the participation of TNFalpha on LPS inhibitory effects, salivary secretion was studied in LPS treated rats after the intraglandular injection of etanercept, a soluble form of TNF receptor which blocks TNFalpha action. Finally, to evaluate the possible interplay between endocannabinoids and TNFalpha on the submandibular gland function reduced during LPS challenge, the salivary secretion was studied after the intraglandular injection of this cytokine alone or concomitantly with AM251 and AM630.


RESULTS
AM251 and AM630, injected separately or concomitantly, partially prevented LPS-induced inhibition of salivation. Also, anandamide synthase activity was increased in submandibular glands extracted from rats 3h after LPS injection, suggesting that the endocannabinoid system was activated in response to this challenge. On the other hand, etanercept, prevented the inhibitory effect of LPS on salivary secretion and moreover, TNFalpha injected intraglandularly inhibited salivary secretion, being this effect prevented by AM251 and AM630 injected concomitantly.


CONCLUSIONS
The present results demonstrate the participation of the endocannabinoid system and TNFalpha on salivary responses during systemic inflammation induced by LPS.
Fernandez-Solari
Javier
J
Cátedra de Fisiología, Universidad de Buenos Aires, Argentina. javierfsolari@yahoo.com.ar
Prestifilippo
Juan Pablo
JP
Ossola
Cesar Angel
CA
Rettori
Valeria
V
Elverdin
Juan Carlos
JC
D000581:Amidohydrolases / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000032:analysis; D001095:Arachidonic Acids / Q000032:analysis; D063385:Cannabinoid Receptor Modulators / Q000502:physiology*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000032:analysis / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids; D000068800:Etanercept; D007074:Immunoglobulin G / Q000494:pharmacology; D007155:Immunologic Factors / Q000494:pharmacology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D018721:Muscarinic Agonists / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides / Q000032:analysis; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors; D043885:Receptor, Cannabinoid, CB2 / Q000037:antagonists & inhibitors; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D012463:Saliva / Q000187:drug effects* / Q000378:metabolism; D012472:Salivation / Q000187:drug effects; D012636:Secretory Rate / Q000187:drug effects; D013363:Submandibular Gland / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology
D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D007074:Immunoglobulin G; D007155:Immunologic Factors; D007211:Indoles; D008070:Lipopolysaccharides; D018721:Muscarinic Agonists; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; D016210:Methacholine Chloride; D005576:Colforsin; D016718:Arachidonic Acid; C103505:AM 251; D000242:Cyclic AMP; D000581:Amidohydrolases; C087226:arachidonoylethanolamide synthase; D000068800:Etanercept; C094023:iodopravadoline; C078814:anandamide