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S. Husain, A.N. Bhat, M.A. Haracznak, D.E. Potter, C.E. Crosson; Natriuretic peptides–induced secretion of matrix metalloproteinases from bovine trabecular meshwork cells . Invest. Ophthalmol. Vis. Sci. 2004;45(13):4664.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Studies have shown that natriuretic peptides lower intraocular pressure in human and animals. However, the underlying cellular mechanism (s) mediating this response remained to be determined. The purpose of these studies was to evaluate the effects of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C–type natriuretic peptide (CNP) on MMPs secretion from bovine trabecular meshwork (BTM) cells. Methods: Primary cultures of bovine TM cells (passages 2–3) were used to examine MMP secretion by Western blotting. Serum starved BTM cells were treated with natriuretic peptides for 6 hr and concentrated medium was analyzed for MMPs using specific anti–MMP–2 and anti–MMP–3 antibodies. Results:ANP increases the secretion of MMP–2 and MMP–3 from BTM cells in a dose dependent manner (MMP–2, EC50: 1.0 x 10–8M, n=4 and MMP–3, EC50: 9.7 x 10–8 M, n=4) when cells were incubated for 6 hr at 37°C. CNP also increases the secretion of MMP–2 and MMP–3 by 44 ±19% and 64 ±24%, respectively. In contrast, BNP had no stimulatory effects on MMP–3 secretion, but moderately increases the secretion of MMP–2 from BTM cells. The overall effects of natriuretic peptides on MMPs secretion from BTM cells were in the following order: ANP>CNP>BNP. The cyclic guanosine monophosphate (cGMP) analog, 8–Br–cGMP increases MMP–2 secretion by 42 ±12% from BTM cells; whereas, MMP–3 secretion was significantly inhibited in the presence of 8–Br–cGMP. Conclusion: The rank order of agonist potency is ANP>CNP>BNP. These data provide evidence that NPR–A receptor is the primary functional natriuretic peptide receptor in the bovine TM cells. The activation of NPR–A receptor leads to the secretion of MMP–2 and MMP–3 via cGMP–independent signaling pathways. These results support the idea that natriuretic peptide–induced increases in outflow facility result, in part, from the NPR–A receptor mediated secretion of MMPs from trabecular meshwork cells.
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