Histamine stimulates secretion of extracellular vesicles with nucleotidase activity in rat submandibular gland

Background: Extracellular vesicles released by different cells have been isolated from diverse fluids including saliva. We previously reported that rat submandibular glands secrete nanovesicles that catalyze hydrolysis of ATP, ADP and AMP, which are actors of the purinergic signaling system along with adenosine. Extracellular nucleotides like ATP and adenosine are involved in the regulation of inflammatory processes and apoptosis. Histamine, a widely distributed biogenic amine, is involved in inflammatory response. Objective: To test if activation of histamine receptors in rat submandibular gland promotes changes in the release of vesicles with nucleotidase activity that could modulate purinergic signaling. Methods: Rat submandibular glands were incubated in the absence or presence of histamine and JNJ7777120, an antagonist for H-4 receptors. Extracellular vesicles were isolated from incubation media by differential centrifugation. Vesicular nucleotidase activity was measured following Pi release by 3 mM MgATP, MgADP or MgAMP. Results: Histamine increased the release of vesicles with nucleotidase activity in a concentration dependent manner: JNJ7777120 significantly reduced this effect. Vesicular nucleotidases obtained in the absence or presence of histamine promoted Pi production from ATP, ADP and AMP. Conclusion: The results show a relationship between histamine and the regulation of purinergic signaling, which could be important in the modulation of inflammatory processes.