The effect of vasoactive intestinal polypeptide (VIP) on protein secretion from lacrimal gland was investigated by using acini prepared by collagenase digestion of rat exorbital lacrimal glands. Protein secretion was determined by incubating the acini for 0-40 min and analyzing the supernatant for peroxidase, a protein secreted by the rat exorbital lacrimal gland. VIP (10(-10) to 10(-7) M) stimulated secretion in a concentration-dependent manner. A maximum concentration of VIP (10(-8) M) stimulated secretion to the same extent as a maximum concentration of carbachol (10(-5) M). The cholinergic antagonist atropine at a concentration (10(-5) M) that completely abolished carbachol-induced secretion did not alter VIP-stimulated secretion. The secretory effects of maximal concentrations of VIP and carbachol were additive, but decreasing the carbachol concentration potentiated secretion. Unlike carbachol, which had no effect on the acinar cAMP level, VIP increased cAMP content sixfold. Immunohistochemical staining demonstrated VIP-like immunoreactivity in nerve fibers throughout the gland, distributed primarily around acini. We conclude that VIP-like immunoreactive nerves are present in the lacrimal gland and that VIP can stimulate protein secretion but utilizes a pathway separate from, but convergent with, that used by cholinergic agonists.

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