title: Cyclic nucleotide-dependent enzyme secretion in the rat lacrimal gland.
abstract: To characterize the role of cyclic nucleotides in secretion of enzymes by the lacrimal gland, pieces of rat exorbital glands were perfused with (1) 8-bromoadenosine-3',5'-cyclic monophosphate (8 Br cyclic AMP), (2) 8-bromoguanosine-3',5'-cyclic monophosphate (8 Br cyclic GMP), (3) forskolin, a stimulator of adenylate cyclase activity, (4) 3-isobutyl-1-methylxanthine (IBMX), an inhibitor of phosphodiesterase activity, or (5) carbachol, a cholinergic agonist. As a measure of enzyme secretion, timed collections of the perifusate effluent were analysed for peroxidase, an enzyme secreted by the lacrimal gland. Control peroxidase secretion was 0.3-0.9 (u./min per milligram protein). Peroxidase secretion was stimulated by 8 Br cyclic AMP (1 mM), but not by 8 Br cyclic GMP (1 mM). A 2-fold increase was detected. Peroxidase secretion was also stimulated by forskolin (60 microM), 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. Finally, Ca2+ depletion in the presence of EGTA (1 mM) inhibited both IBMX-and carbachol-induced secretion by 45% and 60% respectively. We conclude that cyclic AMP, but not cyclic GMP, can stimulate lacrimal gland enzyme secretion. Cyclic AMP appears to utilize a pathway separate from but convergent with cholinergic agonists.
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology; D005576:Colforsin; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D004224:Diterpenes / Q000494:pharmacology; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000378:metabolism; D007765:Lacrimal Apparatus / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D009195:Peroxidase; D010544:Peroxidases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013268:Stimulation, Chemical; D013997:Time Factors
chemical_list: D002316:Cardiotonic Agents; D004224:Diterpenes; D007527:Isoenzymes; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; C016276:8-bromocyclic GMP; D002217:Carbachol; D010544:Peroxidases; D009195:Peroxidase; D006152:Cyclic GMP; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine