Inhibition of salivary secretion by activation of cannabinoid receptors

PRESTIFILIPPO JP; FERNANDEZ SOLARI J; DE LA CAL C; IRIBARNE M; SUBURO AM; RETTORI V; MCCANN S; ELVERDIN JC

Clearwater, Florida

Congreso; XV Symposium on the Cannabinoids; 2005

International Cannabinoid Research Society

The submandibular gland (SMG) is one of the major salivary glands and its secretion is controlled by the autonomic nervous system. End secretory units, called acini, are continuous with a ductal system. Two major signal transduction pathways are implicated in salivary gland cell functions, one involves the generation of cAMP and the other the breakdown of plasma membrane polyphosphoinositides, diacylglycerol and inositol triphosphate. Moreover, increases in the intracellular level of cAMP stimulate various salivary functions, including salivary flow rate and secretion of proteins. Interestingly, most cannabinoid receptors (CB-r) are coupled to G inhibitory protein and respond by inhibiting the activity of adenylyl cyclase. Since it is known that marihuana use decreases saliva secretion, we hypothesized that cannabinoid receptors should be located in salivary glands and could mediate this effect. Therefore, immunohistochemical and physiological studies on SMG of adult male rat were performed. The results showed that both, CB1-r and CB2-r are present in SMG and that they are mainly localized to the ductal system. The in vitro studies incubating SMG in Krebs-Ringer containing the compounds to be tested demonstrated that in the presence of anandamide, forskolin-induced increase of cAMP content was significantly reduced. Moreover, this effect was partially blocked by CB1-r and CB2-r antagonists (AM251 and AM630, respectively), indicating that both receptors are implicated in SMG salivary secretion. Furthermore, in experiment in vivo intraglandularly injected of AEA, inhibited noradrenaline and metacholine-stimulated saliva secretion injected via femoral vein. The inhibitory effect of AEA was prevented significantly by previous injections of AM251 and AM630 intraglandularly. The addition of the antagonists in vitro or the injection into salivary gland in vivo did not affect the cAMP levels nor salivary flow rates. Therefore, we conclude that endocannabinoids control saliva secretion acting through CB1-r and CB2-r localised in SMG. (Supported by BID 1201 OC-AR PICT 14264-03)