The interaction between P2X
7 and muscarinic agonists has been studied in the three types of exocrine glands—lacrimal, pancreas, and salivary. In the only other study on the lacrimal gland, Novak et al.
19 found that cholinergic stimulation leads to the release of ATP, which activates P2X
7 receptors and downregulates the volume of tears produced. The volume of tears indicates electrolyte and water secretion and could come from sources other than the lacrimal gland, although most of the ACh-stimulated fluid secretion is likely from the lacrimal gland. Novak et al.
19 also demonstrated that in the lacrimal gland, cholinergic agonist-stimulated increases in [Ca
2+]
i and fluid (tear) secretion were higher in P2X
7 −/− than in wild-type mice.
19 The effect of P2X
7 receptors was sex dependent because the effect occurred in male, but not in female, mice. Novak et al.
19 concluded that cholinergic agonists release ATP from lacrimal gland acini and small ducts that activate P2X
7 receptors and downregulate tear secretion.
19 In the present study, which used male rat lacrimal glands, activation of the P2X
7 receptors did not alter M
3AChR-stimulated increases in [Ca
2+]
i or protein secretion because the P2X
7 antagonist did not alter muscarinic agonist–stimulated functions and cholinergic agonists did not release ATP from acini. Similar to the Novak et al.
19 study, in preparations that contained duct cells, our results showed that cholinergic agonists caused ATP release. However, in contrast to the Novak et al.
19 study, we found that the activation of muscarinic receptors stimulated the P2X
7 receptor to increase [Ca
2+]
i and to induce protein secretion. The difference between the results of the Novak et al.
19 study and the present study could be species dependent (rat vs. mouse), function dependent (tear volume [electrolyte and water] vs. lacrimal gland protein secretion), or age dependent (8-week-old rats vs. 20- to 40-week-old mice).
19 Given that P2X
7 receptors exist as multiple splice variants, the mechanisms of interaction and activation of the P2X
7 receptor could vary among tissues, species, and sexes.
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