Mechanism of action of calcitonin on secretion in rat submandibular gland.

Calcitonin (CT) was found to reduce the initial flow of pilocarpine-stimulated saliva from the submandibular glands in the rat. Although there was a concomitant increase of the concentration of calcium and protein in the saliva, the calcium/protein ratio was not significantly affected. CT also caused a significant increase of the potassium concentration in submandibular saliva. Both in vivo and in vitro, CT inhibited the production of cyclic AMP (cAMP) both in the absence and in the presence of forskolin. This decrease in intracellular cAMP levels could result in an inhibition of mucus secretion, which would explain the previously observed calcitonin-induced intracellular accumulation of mucus in the submandibular gland acinar cells. CT did not affect the cytoplasmic free Ca2+ concentration (as measured with fura 2) in isolated submandibular acini either in the absence or in the presence of cholinergic or adrenergic agonists. These results indicate that the inhibition of fluid secretion in the submandibular gland by calcitonin must be located distal to changes in [Ca2+]i. It can be concluded that CT affects both mucus and fluid secretion in the submandibular gland, but that only the inhibition of mucus secretion can as yet be explained by an effect at the level of the second messenger.