Beauregard Clay, Brandt Paul C, Chiou George C Y
Department of Medical Pharmacology and Toxicology, College of Medicine, The Texas A&M University System Health Science Center, College Station, Texas 77843 USA.
J Ocul Pharmacol Ther. 2002 Oct;18(5):429-43. doi: 10.1089/10807680260362713.
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.
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.
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).
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.
测试一氧化氮（NO）供体和一氧化氮合酶（NOS）底物通过激活鸟苷酸环化酶来刺激培养的泪腺腺泡细胞分泌蛋白质的用途。
将兔泪腺上皮细胞（RLG细胞）与NO供体和/或NOS底物一起孵育，并用二辛可宁酸测定法测定释放到培养基中的蛋白质。通过测量产生的c-GMP来确定NO前体对鸟苷酸环化酶的激活作用。
NO供体和NOS底物均能够刺激RLG细胞释放蛋白质。在所研究的6种化合物中，硝普钠、硝酸异山梨酯和Nα-苯甲酰-L-精氨酸乙酯（BAEE）释放蛋白质的能力最强，超过基础释放量的100%。这些NO前体刺激了鸟苷酸环化酶的活性，并且被鸟苷酸环化酶抑制剂[1,2,4]恶二唑并-[4,3-a]喹喔啉-1-酮（ODQ）所抑制。
NO供体和NOS底物能够通过激活鸟苷酸环化酶和c-GMP释放来刺激RLG细胞释放蛋白质，而这一过程被鸟苷酸环化酶抑制剂ODQ所阻断。这表明，如果在干眼动物模型中也同样成立，NO供体和NOS底物可用于治疗干眼综合征。
