CB1 and CB2 cannabinoids receptors regulate basal salivation and protein-electrolyte saliva content via modulation of ATPase systems functioning in the acinar cells from submandibular salivary gland

Abstract

We showed that activation in vivo of СВ1 та СВ2 cannabinoids receptors (СBRs) of submandibular salivary gland with selective agonist WIN 55212-2 caused suppression of basal salivation and alteration of saliva content. Similar type of changes were observed after single administration of endocannabinoid and in the conditions of prolonged agonist use. Maximal suppression we observed at 10 min after single application of WIN 55212-2 (~ 45%) and ~ 60% – in the conditions of prolonged administration of an agonist. Prolonged treatmnent with WIN 55212-2 leads to acidification of secreted saliva (рН ~ 9.0-8.8), increase in saliva Ca2+ and protein concentration as well as α-amylase activity. Any significant changes of K+, Na+, P2+ concentrations in saliva were observed upon activation of СBRs. We also showed that decrease of basal salivation is accompanied by inhibition of Na+/K+-АТP-ase and endoplasmic reticulum Са2+-АТP-ase but increased activity of plasma membrane Са2+-АТP-ase. Therefore upon activation of СBRs: і) c-АМP-mediated signaling system that contribute to the protein secretion increases activity; іі) transcellular H2O transport that contribute to the fluid secretion is reduced forming the base of inbition of basal salivation; ііі) electrolyte saliva content remains unaltered that can be attributed to the unaltered functioning of the ductal cells unlike acinar cells. Concluding, we suggest that observed changes of saliva рН and activity of АТP-ase systems in acinar cells contribute to the СBRs-mediated inhibition of basal salivation provided by submandibular salivary gland.

Keywords

• cannabinoid receptors
• win 55212-2
• submandibular salivary gland
• salivation
• atp-ase activity