Inhibition of salivary secretion by activation of endocannabinoid receptors

JUAN PABLO PRESTIFILIPPO; JAVIER FERNÁNDEZ-SOLARI; CAROLINA DE LA CAL; MARÍA IRIBARNE; ANGELA M. SUBURO; VALERIA RETTORI; SAMUEL M. MCCANN; JUAN CARLOS ELVERDIN

Experimental Biology and Medicine

Society for the Experimental Biology and Medicine

Año: 2006 vol. 231 p. 1421 - 1429

1535-3702

It is known that marihuana use decreases saliva secretion. Therefore, we hypothesized that cannabinoid receptors (CB-rs) are located in salivary glands to mediate that effect. In these experiments we used the submandibular gland (SMG) that is one of the major salivary glands. Mammalian tissues contain at least two types of CB-rs, CB1-r and CB2-r, mainly located in the nervous system and peripheral tissues, respectively. Both receptors are coupled to protein Gi and respond by inhibiting the activity of adenylyl cyclase (AC). We demonstrated that both CB1-r and CB2-r are present in the SMG, each showing specific localizations. The best known endocannabinoid is anandamide (AEA) that binds with high affinity to both CB-rs. We showed that AEA markedly reduced forskolin-induced increase of cAMP content in vitro. This effect was blocked by AM251 or AM630 (CB1-r and CB2-r antagonists, respectively), indicating that both receptors are implicated in SMG physiology. Additionally, we showed that AEA injected intraglandularly inhibited norepinephrine (NE) and metacholine (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 co-injection with AM630. Therefore, we concluded that AEA decreases saliva secretion in SMG acting through CB1 and CB2 receptors.