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ORIGINAL RESEARCH ARTICLE

Inhibition of Salivary Secretion by Activation of Cannabinoid Receptors

Juan Pablo Prestifilippo^*,,1, Javier Fernández-Solari^*,, Carolina de la Cal, María Iribarne, Angela M. Suburo, Valeria Rettori^*, Samuel M. McCann^* and Juan Carlos Elverdin

^* Centro de Estudios Farmacológicos y Botánicos (CEFYBO-CONICET), Buenos Aires 1121, Argentina; Cat de Fisipatología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires 1121, Argentina; Cat de Fisiología, Facultad de Odontología, Universidad de Buenos Aires, Buenos Aires 1121, Argentina; and Cat de Medicina celular y Molecular, Universidad Austral, Buenos Aires 1121, Argentina

To whom requests for reprints should be addressed at ¹ Centro de Estudios Farmacológicos y Botánicos (CEFYBO-CONICET) (ex CIBIER), Paraguay 2155, piso 16, Ciudad de Buenos Aires, Buenos Aires 1121, Argentina. E-mail: jprestifilippo{at}yahoo.com.ar

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.

Key Words: anandamide • submandibular gland • cAMP • AM251 • AM630

This article has been cited by other articles:

				M. Iribarne, V. Torbidoni, K. Julian, J. P. Prestifilippo, D. Sinha, V. Rettori, A. Berra, and A. M. Suburo Cannabinoid Receptors in Conjunctival Epithelium: Identification and Functional Properties Invest. Ophthalmol. Vis. Sci., October 1, 2008; 49(10): 4535 - 4544. [Abstract] [Full Text] [PDF]