title: Inhibition of salivary secretion by activation of cannabinoid receptors.
abstract: It is known that marijuana use decreases saliva secretion. Therefore, we hypothesized that cannabinoid receptors (CBs) are located in salivary glands to mediate that effect. In these experiments, we used the submandibular gland (SMG) of male rats, which is one of the major salivary glands. Mammalian tissues contain at least two types of CBs, CB1 and CB2, mainly located in the nervous system and peripheral tissues, respectively. Both receptors are coupled to Gi protein and respond by inhibiting the activity of adenylyl cyclase. We demonstrated that both CB1 and CB2 are present in the SMG, each showing specific localizations. The best-known endocannabinoid is anandamide (AEA), which binds with high affinity to CB1 and CB2. We showed that AEA markedly reduced forskolin-induced increase of cAMP content in vitro. This effect was blocked by AM251 and AM630 (CB1 and CB2 antagonists, respectively), indicating that both receptors are implicated in SMG physiology. In addition, we showed that AEA injected intraglandularly to anesthetized rats inhibited norepinephrine (NE)- and methacholine (MC)-stimulated saliva secretion in vivo and that both AM251 or AM630 prevented the inhibitory action of AEA. Also, the intraglandular injection of AM251 increased saliva secretion induced by lower doses of NE or MC. This increase was synergized after coinjection with AM630. Therefore, we concluded that AEA decreases saliva secretion in the SMG acting through CB1 and CB2 receptors.
authors.affiliation: Centro de Estudios Farmacológicos y Botánicos (CEFYBO-CONICET) (ex CIBIER), Paraguay 2155, piso 16, Ciudad de Buenos Aires, Buenos Aires 1121, Argentina. jprestifilippo@yahoo.com.ar
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Prestifilippo
authors.forename: Javier
authors.initials: J
authors.lastname: Fernández-Solari
authors.forename: Carolina
authors.initials: C
authors.lastname: de la Cal
authors.forename: María
authors.initials: M
authors.lastname: Iribarne
authors.forename: Angela M
authors.initials: AM
authors.lastname: Suburo
authors.forename: Valeria
authors.initials: V
authors.lastname: Rettori
authors.forename: Samuel M
authors.initials: SM
authors.lastname: McCann
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Elverdin
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000008:administration & dosage*; D063385:Cannabinoid Receptor Modulators / Q000008:administration & dosage*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D063388:Endocannabinoids; D007150:Immunohistochemistry; D007211:Indoles / Q000494:pharmacology; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010277:Parasympathomimetics / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043882:Receptors, Cannabinoid / Q000187:drug effects* / Q000378:metabolism*; D012463:Saliva / Q000187:drug effects / Q000378:metabolism*; D013363:Submandibular Gland / Q000378:metabolism*; D013566:Sympathomimetics / Q000494:pharmacology
chemical_list: D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D007211:Indoles; D010277:Parasympathomimetics; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D013566:Sympathomimetics; D016210:Methacholine Chloride; D005576:Colforsin; C103505:AM 251; D000242:Cyclic AMP; C094023:iodopravadoline; C078814:anandamide; D009638:Norepinephrine