Cyclic nucleotide-dependent enzyme secretion in the rat lacrimal gland.

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Abstract
To characterize the role of cyclic nucleotides in secretion of enzymes by the lacrimal gland, pieces of rat exorbital glands were perfused with 8-bromo-cAMP (8 Br cAMP), 8-bromo-cGMP (8 Br cGMP), forskolin, a stimulator of adenylate cyclase activity, 3-isobutyl-1-methylxanthine (IBMX), an inhibitor of phosphodiesterase activity or carbachol, a cholinergic agonist. As a measure of enzyme secretion, timed collections of the perifusate effluent were analyzed for peroxidase, an enzyme secreted by the lacrimal gland. Control peroxidase secretion was 0.3-0.9 (U/min per mg protein). Peroxidase secretion was stimulated by 8 Br cAMP (1 mM), but not by 8 Br cGMP (1 mM). A 2-fold increase was detected. Peroxidase secretion was also stimulated by forskolin (60 .mu.M), IBMX (1 mM), and the cholinergic agonist carbachol, which all stimulated peroxidase secretion 2- or 3-fold. The effect of maximally effective concentrations of IBMX (1 mM) and carbachol (0.1 mM) on secretion was additive. Ca2+ depletion in the presence of EGTA [ethyleneglycol-bis-(.beta.-aminoethylether)-N,N,N'',N''-tetraacetic acid] (1 mM) inhibited both IBMX- and carbachol-induced secretion by 45 and 60%, respectively. Cyclic AMP, but not cGMP, can apparently stimulate lacrimal gland enzyme secretion. Cyclic AMP appears to utilize a pathway separate from but convergent with cholinergic agonists.