Purchase this article with an account.
P.W. Yates, S. Husain, J.A. Fant, C.E. Crosson; The Adenosine A1 Agonist Cyclohexyladenosine Increases MMP Secretion in Human Ciliary Muscle Cells . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2617.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
The objective of this study was to investigate the effects of adenosine A1 agonist, N6–cyclohexyladenosine (CHA), on matrix metalloproteinase (MMP) secretion in human ciliary muscle (HCM) cells.
To evaluate MMP secretion, primary cultures of HCM cells were serum–starved for 16 hours and treated with CHA (1 µmol/L) for 2 – 24 hours. Culture media was then collected and MMPs analyzed by Western blotting. The activation of extracellular regulated kinase 1 and 2 (ERK1/2) was determined by Western blotting of cellular lysates. To determine the effects of receptor antagonists and pathway inhibitors, agents were administered one hour prior to the addition of CHA.
The addition of CHA (1 µmol/L) for two hours significantly increased the secretion of MMP–2 by 69 ± 10% over control levels. The addition of CHA for 24 hours significantly increased the secretion of MMP–1 by 102 ± 24 and MMP–3 by 138 ± 29% over control levels. Pretreatment with adenosine A1 receptor antagonist, CPT (10 µmol/L) or ERK pathway inhibitor U–0126 (1 µmol/L) significantly reduced the CHA–induced secretion of MMPs. In addition, CHA (1 µmol/L) increased the ERK1/2 activation by 102 ± 13%, and this response was blocked by pretreatment with CPT (10 µmol/L).
These results provide evidence for the existence of functional adenosine A1 receptors in human ciliary smooth muscle cells. The stimulation of these receptors leads to the secretion of multiple MMPs and these secretory events are dependent on the activation of ERK1/2 pathways. As adenosine receptor agonists have been shown to lower IOP in a variety of animal models and humans, our data support the idea that the ocular hypotension induced by adenosine A1 agonists results in part from the increase in uveoscleral outflow.
This PDF is available to Subscribers Only