섬유주세포에서 국소 탄산탈수효소억제제가일산화질소의 생성에 미치는 영향에 대한 연구
The Effects of Topical Carbonic Anhydrase Inhibitors on Nitric Oxide Production in Trabecular Meshwork Cells
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목적: 섬유주세포에서 국소 탄산탈수효소억제제가 일산화질소의 생성에 미치는 영향과 차이를 알아 보고자 하였다. 대상과 방법: 섬유주세포를 일차배양한 후 혈청이 포함되지 않은 배지를 이용하여 0, 10, 100 μM의 도르졸라미드와 브린졸라미드에각각 3일간 노출시킨 후 Griess assay를 이용하여 일산화질소의 생성량을 측정하였으며, RT-PCR을 이용하여 eNOS mRNA의 발현을조사하였다. 결과: 10, 100 μM의 도르졸라미드와 브린졸라미드는 섬유주세포에서 일산화질소의 생성을 유의하게 증가시켰으며(p＜0.05), eNOSmRNA의 발현을 증가시켰다. 도르졸라미드가 브린졸라미드에 비해 더 유의하게 일산화질소를 생성하였으며 eNOS mRNA의 발현도증가시켰다. 결론: 섬유주세포에서 국소 탄산탈수효소억제제는 일산화질소의 생성과 발현을 증가시켰으며 도르졸라미드가 브린졸라미드에 비해 더유의하게 일산화질소의 생성을 증가시켰다. 따라서 국소 탄산탈수효소억제제는 탄산탈수효소저해작용 외에 또 다른 작용기전에 의해효과를 나타낼 것으로 생각된다.
Abstract
Purpose: To investigate and compare the effects of topical carbonic anhydrase inhibitors on the production and expressionof nitric oxide in cultured human trabecular meshwork cells (HTMC). Methods: Primarily cultured HTMC were exposed to 0, 10, and 100 μM dorzolamide and brinzolamide using serum-deprivedmedia for 3 days. Production of nitric oxide was assessed with Griess assay. Expressions of eNOS mRNA were assessedwith RT-PCR. Results: Both dorzolamide and brinzolamide increased the production of nitric oxide eNOS activity (p < 0.05). Dorzolamidehad a more potent effect than brinzolamide on the production of nitric oxide and the expression of eNOS mRNA. Conclusions: Topical carbonic anhydrase inhibitors increased the production of nitric oxide, which was accompanied by increasedeNOS activity. Dorzolamide had a more potent effect than brinzolamide on the production of nitric oxide and expressionof eNOS mRNA in HTMC. The increased production of nitric oxide by topical carbonic anhydrase inhibitors involvesmechanisms other than carbonic anhydrase inhibition.
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