The physiological and pharmacological responses of an ex vivo mouse submandibular gland were used to study fluid secretion and cell signaling in response to muscarinic stimulation at increasing temperatures. Saliva production at 37°C was 5.5-fold that at 25°C with pilocarpine stimulation and 9.8-fold that at 25°C with cevimeline stimulation. Both of these muscarinic agonists are used clinically. With the experimental agonist carbachol (CCh), saliva secretion was increased with an increase in temperature, but the CCh concentration producing the peak flow was the same in both dose-response curves, suggesting that the muscarinic receptor itself is not responsible for the temperature dependence. Purinergic agonists also induced temperature-dependent saliva production ex vivo. The calcium ionophore A23187 failed to have a significant effect on saliva production. The CCh-induced increase in intracellular Ca2+ also upregulated the initial increase and sustained the plateau phase of saliva flow. Thus, muscarinic receptor stimulation of saliva production is temperature sensitive due to an increase in intracellular Ca2+.
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