Nitric oxide and cyclic GMP-mediated protein secretion from cultured lacrimal gland acinar cells.
OBJECTIVE
Nitric oxide (NO) donors and NO synthase (NOS) substrates were tested for their use to stimulate protein secretion from cultured lacrimal gland acinar cells, through activation of guanylate cyclase.


METHODS
Rabbit lacrimal gland epithelial cells (RLG cells) were incubated with NO donors and/or NOS substrates and the protein released into culture medium was determined with bicinchoninic acid assay. Guanylate cyclase activation by NO precursors was determined by measurement of c-GMP produced.


RESULTS
Both NO donors and NOS substrates were able to stimulate protein release from RLG cells. Among 6 compounds studied, sodium nitroprusside, isosorbide dinitrate and N(a)-benzoyl L-arginine ethyl ester (BAEE) were most potent to release protein over 100% of the basal release. The guanylate cyclase activity was stimulated by these NO precursors and was inhibited by guanylate cyclase inhibitor, [1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ).


CONCLUSIONS
NO donors and NOS substrates were able to stimulate protein release from RLG cells via activation of guanylate cyclase and c-GMP release, which was blocked by guanylate cyclase inhibitor, ODQ. It indicates that NO donors and NOS substrates could be used for the treatment of dry eye syndrome if the same holds true in dry eye animal models.
Beauregard
Clay
C
Department of Medical Pharmacology and Toxicology, College of Medicine, The Texas A&M University System Health Science Center, College Station, Texas 77843 USA.
Brandt
Paul C
PC
Chiou
George C Y
GC
D000818:Animals; D002461:Cell Line, Transformed; D006152:Cyclic GMP / Q000096:biosynthesis*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005136:Eye Proteins / Q000378:metabolism*; D007765:Lacrimal Apparatus / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011817:Rabbits
D004791:Enzyme Inhibitors; D005136:Eye Proteins; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP