Efects of premedication on salivary secretion in rat submandibular gland

Objectives: Parasympathetic antagonists are frequently used for premedication to reduce saliva secretion and bradycardia. Glycopyrrolate is said to have similar antisialagogue effects, but is less likely to cause significant tachycardia than atropine. Different antimuscarinic receptor selectivity patterns could explain the differences. The aim of this study was to determine the effects of antagonists on salivary secretion from the submandibular gland evoked by acetylcholine. Methods: Male Wistar rats, weighing 250-280 g, were used. Pirenzepine, methoctramine, 4-DAMP and glycopyrrolate were infused intravenously, in rat at various dose levels. After administration of drags, we tested salivary flow rate, amylase activity. Results: 4-DAMP markedly inhibited the acetylcholine-evoked fluid responses. Pirenzepine showed significantly lower inhibitory potency than 4-DAMP, while methoctoramine and glycopyrrolate exerted an even lesser inhibitory effect. Pirenzepine reduced the protein concentration in the submandibular saliva. While 4-DAMPsignificantly inhibited acetylcholine-evoked protein secretory responses, methoctramine and glycopyrrolate affected the responses. We found a decrease in acetylcholine-evoked saliva flow and amylase activity after muscarinic antagonists injection. The amount of saliva secreted from the submandibular gland was dose dependent. The salivary amylase activity was higher at the highest dose. In response to the highest dose, but not the lower doses, the total glandular amylase activity and the numerical density of submandibular acinar secretory granules were lowered, by 23% and 22%, respectively. The reduction of the protein concentration in submandibular saliva caused by 4-DAMP and pirenzepine was inhibited by L-NAME. Conclusion: Thus in addition to M3receptors, other muscarinic receptors contribute to in vivo functional responses in rat submandibular gland. However, M1 receptors may induce indirect effects via nitric oxide in the submandibular gland. In the rat submandibular gland, which use Ca2+ as a second messenger, may release proteins not only by non-granular mechanisms but also, and in contrast to the general belief, by granule exocytosis.