Role of the endocannabinoid system in ethanol-induced inhibition of salivary secretion.
OBJECTIVE
The aim of the present study was to determine whether the endocannabinoid system could be involved in the ethanol-induced inhibition of salivation in adult male Wistar rats.


METHODS
Salivary secretion induced by different concentrations of methacholine, a cholinergic agonist, and the endocannabinoid arachidonoyl ethanolamide (anandamide, AEA) production in the submandibular gland (SMG) were determined in rats after ethanol (3 g/kg) administration by gastric gavage. To study the participation of cannabinod receptors in ethanol action, we evaluated methacholine-induced salivary secretion after ethanol administration when CB1 or CB2 receptors were blocked by intra-SMG injections of their selective antagonists AM251 and AM630, respectively. Additionally, we evaluated the in vitro effect of ethanol (0.1 M) on SMG production of cAMP, alone or combined with AM251 or AM630.


RESULTS
Acute ethanol administration increased AEA production in SMG and also inhibited the methacholine-induced saliva secretion that was partially restored by intraglandular injection of AM251 or AM630. In addition, ethanol significantly reduced the forskolin-induced increase in cAMP content in SMG in vitro while treatment with AM251 blocked this response.


CONCLUSIONS
We conclude that the inhibitory effect produced by ethanol on submandibular gland salivary secretion is mediated, at least in part, by the endocannabinoid system.
Prestifilippo
Juan Pablo
JP
Cátedra de Fisiología, Universidad de Buenos Aires, Argentina. jprestifilippo@yahoo.com.ar
Fernández-Solari
Javier
J
Medina
Vanina
V
Rettori
Valeria
V
Elverdin
Juan Carlos
JC
D000818:Animals; D001095:Arachidonic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D063385:Cannabinoid Receptor Modulators / Q000008:administration & dosage / Q000494:pharmacology*; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000494:pharmacology*; D005576:Colforsin / Q000037:antagonists & inhibitors; D000242:Cyclic AMP / Q000235:genetics; D063388:Endocannabinoids; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D016210:Methacholine Chloride / Q000008:administration & dosage / Q000494:pharmacology*; D018721:Muscarinic Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology; D053284:Polyunsaturated Alkamides / Q000008:administration & dosage / Q000494:pharmacology*; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043885:Receptor, Cannabinoid, CB2 / Q000037:antagonists & inhibitors; D012463:Saliva / Q000187:drug effects* / Q000378:metabolism*; D012472:Salivation / Q000187:drug effects*; D013363:Submandibular Gland / Q000187:drug effects*
D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D002492:Central Nervous System Depressants; D063388:Endocannabinoids; D007211:Indoles; D018721:Muscarinic Agonists; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles; D043885:Receptor, Cannabinoid, CB2; D016210:Methacholine Chloride; D005576:Colforsin; C103505:AM 251; D000431:Ethanol; D000242:Cyclic AMP; C094023:iodopravadoline; C078814:anandamide